Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

ADVANCED POLYMER NANOPARTICLES Synthesis and Surface Modifications

ADVANCED POLYMER NANOPARTICLES Synthesis and Surface Modifications

Edited by

Vikas Mittal

Boca Raton London New York

CRC Press is an imprint of the Taylor & Francis Group, an informa business

CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2011 by Taylor and Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number: 978-1-4398-1443-7 (Hardback) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright. com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data Advanced polymer nanoparticles : synthesis and surface modifications / [edited by] Vikas Mittal. p. cm. “A CRC title.” Includes bibliographical references and index. ISBN 978-1-4398-1443-7 (hardcover : alk. paper) 1. Polymerization. 2. Nanoparticles. 3. Polymers--Surfaces. I. Mittal, Vikas. II. Title. TP156.P6A38 2011 620.1’92--dc22 Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com

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Contents Preface..................................................................................................................... vii Editor........................................................................................................................ix Contributors.............................................................................................................xi 1. Polymer Latex Technology: An Overview..................................................1 V. Mittal 2. Synthesis of Polymer Particles with Core-Shell Morphologies........... 29 Claudia Sayer and Pedro Henrique Hermes de Araújo 3. Advanced Polymer Nanoparticles with Nonspherical Morphologies.................................................................................................. 61 Yongxing Hu, Jianping Ge, James Goebl, and Yadong Yin 4. Block, Graft, Star, and Gradient Copolymer Particles........................... 97 H. Matahwa, E. T. A. van den Dungen, J. B. McLeary, and B. Klumperman 5. Polymer Nanoparticles by Reversible Addition-Fragmentation Chain Transfer Microemulsion Polymerization................................... 133 J. O’Donnell and E. Kaler 6. pH-Responsive Polymer Nanoparticles.................................................. 169 Jonathan V. M. Weaver 7. Smart Thermo-Responsive Nanoparticles............................................. 197 Peng Tian and Qinglin Wu 8. Surface Tailoring of Polymer Nanoparticles with Living Polymerization Methods............................................................................ 223 Koji Ishizu and Dong Hoon Lee 9. Effects of Nano-Sized Polymerization Locus on the Kinetics of Controlled/Living Radical Polymerization............................................ 263 Hidetaka Tobita 10. Functional Polymer Particles by Emulsifier-Free Polymerization.... 307 V. Mittal

v

vi

Contents

11. Polymer Nanoparticles with Surface Active Initiators and Polymer Initiators........................................................................................ 329 Klaus Tauer Index...................................................................................................................... 361

Preface Polymer latex particles are a very important class of polymeric materials, which are used for a large number of commercial applications. These particles are synthesized in the aqueous dispersion phase by numerous synthesis methodologies such as emulsion, miniemulsion, microemulsion, dispersion, suspension, inverse emulsion (in organic phase), polymerization, etc. Over the years, significant enhancement in the techniques dealing with the synthesis and surface tailoring of polymer particles has been achieved, which has also resulted in the widening of the application spectrum of these particles. These advances include use of advanced controlled polymerization means such as nitroxide-mediated polymerization, atom transfer radical polymerization, radical addition fragmentation transfer polymerization, etc., as well as use of advanced stabilizers, surface modifiers, etc. These advances have made it possible to achieve polymer particles with specific sizes consisting of polymer chains of specific molecular weights and tailorable chemical compositions or properties according to the requirement. Because the advanced synthesis techniques are the key to achieve new functional properties in the polymer nanoparticles, and the surface modifications of these particles are required to ensure their use for specific applications, it is of immense importance to bring readers up-to-date on recent advances in these fields. This information will enable readers to design the required particle systems. This book thus serves the purpose of summarizing the developments in the synthesis and surface modification techniques to generate advanced polymer particles, and the contents have been accordingly organized. Chapter 1 introduces polymer latex technology with an overview of the various conventional and recent synthesis methodologies. Synthesis and characterization of particles with core-shell morphol­ogies have been focused on in Chapter 2. Chapter 3 reports the generation of nonspherical polymer particles by following different synthetic routes. The generation of specific architectures such as block, star, graft, and gradient copolymer particles has been detailed in Chapter 4. Microemulsion polymerization using reversible addition-fragmentation chain transfer controlled radical polymerization is the subject of Chapter 5. In Chapter 6, pH-responsive nanoparticles have been described, whereas the synthesis of smart thermally responsive particles has been reported in Chapter 7. Surface tailoring of various organic and inorganic nanoparticles by polymers is the subject of Chapter 8. Theoretical studies on the kinetics of controlled radical polymerization techniques have been explained in Chapter 9. Chapter 10 reports the synthesis of functional nanoparticles by using the ­surfactant-free emulsion polymerization vii

viii

Preface

approach. Chapter 11 describes various surface-active initiators as well as polymeric stabilizers developed for polymer nanoparticles in recent years. At this juncture, I would like to express my heartfelt thanks to Taylor & Francis Group for their kind support during the project. I am equally thankful to Professor Massimo Morbidelli at the Swiss Federal Institute of Technology, Zurich, Switzerland, who has been my guide in polymer latex technology. I am indebted to my family, especially my mother, whose continuous support and motivation have made this work feasible. I dedicate this book to my dear wife Preeti, for her valuable help in coediting the book as well as for her efforts in improving the quality of the book. Vikas Mittal Ludwigshafen, Germany

Editor Dr. Vikas Mittal studied chemical engineering at Punjab Technical Univer­ sity in Punjab, India. He later obtained his master of technology in polymer science and engineering from the Indian Institute of Technology, Delhi, India. Subsequently, he joined Professor U. W. Suter’s polymer chemistry group at the Department of Materials at the Swiss Federal Institute of Technology, Zurich, Switzerland, where he worked for his doctoral degree with a focus on the subjects of surface chemistry and polymer nanocomposites. He also jointly worked with Professor M. Morbidelli at the Department of Chemistry and Applied Biosciences on the synthesis of functional polymer latex particles with thermally reversible behaviors. After completion of his doctoral research, Dr. Mittal joined the Active and Intelligent Coatings section of Sun Chemical Group Europe in London. He worked for the development of water- and solvent-based coatings for food-packaging applications. He later joined BASF Polymer Research in Ludwigshafen, Germany, as a polymer engineer, where he is currently working as a laboratory manager responsible for the physical analysis of organic and inorganic colloids. His research interests include organic–inorganic nanocomposites, novel filler surface modifications, thermal stability enhancements, polymer latexes with functionalized surfaces, etc. He has authored more than 40 scientific publications, book chapters, and patents on these subjects.

ix

Contributors

Pedro Henrique Hermes de Araújo Department of Chemical Engineering Federal University of Santa Catarina Florianópolis, Brazil

Dong Hoon Lee Department of Organic Materials and Macromolecules Tokyo Institute of Technology Tokyo, Japan

Jianping Ge Department of Chemistry University of California–Riverside Riverside, California

H. Matahwa Department of Chemistry and Polymer Science University of Stellenbosch Matieland, South Africa

James Goebl Department of Chemistry University of California–Riverside Riverside, California Yongxing Hu Department of Chemistry University of California–Riverside Riverside, California Koji Ishizu Department of Organic Materials and Macromolecules Tokyo Institute of Technology Tokyo, Japan E. Kaler Stony Brook University Stony Brook, New York B. Klumperman Department of Chemistry and Polymer Science University of Stellenbosch Matieland, South Africa and Lab of Polymer Chemistry Eindhoven University of Technology Eindhoven, the Netherlands

J. B. McLeary Plascon Research Centre University of Stellenbosch Matieland, South Africa V. Mittal Polymer Research BASF SE Ludwigshafen, Germany and Department of Chemistry and Applied Biosciences Institute of Chemical and Bioengineering ETH Zurich Zurich, Switzerland J. O’Donnell Iowa State University Ames, Iowa Claudia Sayer Department of Chemical Engineering Federal University of Santa Catarina Florianópolis, Brazil xi

xii

Contributors

Klaus Tauer Department of Colloid Chemistry Max Planck Institute of Colloids and Interfaces Golm, Germany

E. T. A. van den Dungen Department of Chemistry and Polymer Science University of Stellenbosch Matieland, South Africa

Peng Tian School of Renewable Natural Resources Louisiana State University Baton Rouge, Louisiana

Jonathan V. M. Weaver Department of Chemistry University of Liverpool Liverpool, United Kingdom

Hidetaka Tobita Department of Materials Science and Engineering University of Fukui Fukui, Japan

Qinglin Wu School of Renewable Natural Resources Louisiana State University Baton Rouge, Louisiana

Yadong Yin Department of Chemistry University of California–Riverside Riverside, California

1 Polymer Latex Technology: An Overview*

V. Mittal Contents 1.1 Introduction.....................................................................................................1 1.2 Emulsion Polymerization..............................................................................2 1.3 Controlled Polymerization and its Use in Emulsion Polymerization Processes..............................................................................9 1.4 Conventional and Controlled Miniemulsion Polymerization................ 16 1.5 Generation of Copolymer or Core-Shell Particles.................................... 20 References................................................................................................................ 25

1.1 Introduction Polymer nanoparticles find use in a number of applications like coatings, adhesives, paints, etc. The applications of these nanoparticles are significantly affected by their physical properties as well as surface morphology, which can be controlled by the synthesis process used to generate such particles. Emulsion poly­mer­i­za­tion and its modified methodologies are the most commonly used techniques to achieve poly­mer nanoparticles. These techniques also allow the generation or surface functionalization of the particles either in situ or by following separate specific steps. Polymerization of monomer by emulsion poly­mer­i­za­tion offers significant advantages in the whole poly­mer­ i­za­tion process as compared to bulk and solution poly­mer­i­za­tion methods. It allows better control of the heat and viscosity of the system, and emulsion poly­mer­i­za­tion allows the achievement of an increase in molecular weight of the poly­mer chains without negatively impacting the rate of poly­mer­i­za­tion [1]. In emulsion poly­mer­i­za­tion, most of the monomer is present as monomer droplets in the aqueous phase, which diffuses to the polymerizing particles during the course of poly­mer­i­za­tion. The diffusion of the monomer is *

The work was carried out at Institute of Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.

1

2

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

possible when the monomer is partially water soluble. Thus, emulsion poly­ mer­i­za­tion is not very effective with extremely hydrophobic and extremely hydrophilic monomers. The extremely hydrophobic monomers would always stay in the monomer droplets, leading to no poly­mer­i­za­tion, whereas the hydrophilic monomers would poly­mer­ize mainly by homogenous poly­mer­ i­za­tion and not micellar poly­mer­i­za­tion. To circumvent these difficulties, miniemulsion poly­mer­i­za­tion is used [2,3]. In this technique, the diffusion of the monomer molecules through the aqueous phase is not required, as the monomer droplets are directly poly­mer­ized. Therefore, such a technique has no problem in achieving the poly­mer­i­za­tion of even extremely hydrophobic monomers. To poly­mer­ize very hydrophilic monomers, inverse miniemulsion can be used. Combination of controlled poly­mer­i­za­tion methods like nitroxide-mediated poly­mer­i­za­tion, atom transfer radical poly­mer­i­za­tion, and reversible addition fragmentation chain transfer poly­mer­i­za­tion with the emulsion and miniemulsion poly­mer­i­za­tion methods has further enhanced the possibilities of achieving functional poly­mer particles [4]. By using these techniques, synthesis of functional block copolymer or graft copolymer particles can be achieved, which is not possible by using conventional emulsion poly­mer­i­za­tion techniques owing to the very short lifetime of the radicals. The surface morphologies of the particles can also be efficiently controlled or tuned by using such controlled poly­mer­i­za­tion methods, which expands the spectrum of application of these particles. This chapter aims to provide an overview of the conventional emulsion poly­mer­i­za­tion methods and the more advanced methods of synthesizing poly­mer particles.

1.2 Emulsion Polymerization Emulsion poly­mer­i­za­tion is a heterogeneous poly­mer­i­za­tion technique that uses water as dispersion medium for the poly­mer­i­za­tion of water-insoluble monomers in the form of suspended particles. Styrene, methyl methacrylate, butyl acrylate, etc. are examples of the most commonly used monomers for the generation of polymers by emulsion poly­mer­i­za­tion. The surfactants are generally used to provide colloidal stability to the system. The surfactant can be cationic, anionic, or nonionic, and its amount exceeds the critical micelle concentration significantly. The surfactants form micelles in the system in which the poly­mer­i­za­tion takes place. Thus, this process can be visualized as a bulk poly­mer­i­za­tion in each of the suspended particles. Polymerization by this mode helps to circumvent the problems of heat and viscosity control generally associated with bulk poly­mer­i­za­tion. By changing the amount of surfactant, the molecular weight of the poly­mer chains can be increased without decreasing the poly­mer­i­za­tion rate, which is not possible in other modes of poly­mer­i­za­tion. The presence of a significant amount of surfactant

3

Polymer Latex Technology: An Overview

in the system can lead to certain disadvantages; however, many applications of particles are not affected by the presence of surfactants. Surfactant-free poly­mer­i­za­tion can also be used to generate poly­mer particles in order to circumvent the problems associated with the use of emulsifier, but in this case, the mode of poly­mer nucleation is completely different. As mentioned previously, the amount of the surfactant exceeds the critical micelle concentration in the emulsified emulsion poly­mer­i­za­tion process. The micelles formed as a result of this excess amount have a size in the range of 10 nm, and one micelle generally consists of 100–200 surfactant molecules [1]. Surface tension of the solution decreases with the addition of surfactant at critical micelle concentration. A host of other solution properties are also affected at critical micelle concentration of the surfactant, which include conductivity, turbidity, osmotic pressure, etc. [5]. However, in the emulsion poly­mer­i­za­tion process, it is the reduction in the surface tension of the aqueous phase that is of prime importance. Because surfactants are amphiphilic molecules containing one hydrophobic part and one hydrophilic part, in the micelle they orient themselves in a way so that the hydrophobic part forms the inner part of the micelle and the hydrophilic part radiates away from this inner part of the micelle into the aqueous phase. The resulting hydrophobic space inside the micelle owing to the self-assembly of the surfactant molecules is an ideal place for the hydrophobic monomer to reside and also provides an ideal environment for the radicals to enter the micelle. Figure 1.1 shows the representation of the association of the surfactant molecules after the critical micelle concentration of the surfactant is reached [6]. When the inverse emulsion poly­mer­i­za­tion is used, then the hydrophilic part of the surfactant forms the inner part of the micelles and the hydrophilic chains intermix with the organic dispersion phase.

(a)

(b)

Figure 1.1 Organization of the surfactant molecules (a) below and (b) above the critical micelle concentration of the surfactant in the aqueous solution.

4

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

The monomers used for emulsion poly­mer­i­za­tion are water insoluble (water soluble for inverse emulsion poly­mer­i­za­tion). However, the monomer should have some extent of water solubility in order to diffuse through the aqueous phase as required during the course of poly­mer­i­za­tion. When the monomer is added to the system, a part of the monomer enters the micelles and a part is dissolved in the aqueous phase owing to partial water solubility. However, the majority of the monomer is present in the form of monomer droplets. The size of the monomer droplets is much larger than that of micelles; however, their number is much lower as compared to the micelles. Water-soluble initiators are generally used to initiate the poly­mer­i­za­tion reaction. The initiator generates the radicals in the aqueous phase owing to thermal dissociation. The generated radicals have the possibility of entering either the micelles or the monomer droplets. However, experimental evidence proves the absence of droplet poly­mer­i­za­tion. The radicals do not enter the monomer droplets, as the radical entities are hydrophilic in nature whereas the monomer droplets are hydrophobic. Also, because the number of monomer droplets is much smaller than the number of micelles, it is micelles that capture the majority of the radicals. Also, the unique architecture of the micelles provides attractive conditions for the radicals to enter. Figure 1.2a shows the mechanism of the micellar nucleation for the generation of poly­mer particles. This mode of nucleation is also termed heterogeneous nucleation. The homogenous mode of particle nucleation is also possible when (a) the amount of surfactant is below its critical micelle concentration, (b) no surfactant is used during the poly­mer­i­za­tion, or (c) the monomer is significantly water soluble. In this mode of nucleation, the generated radicals in the aqueous phase start reacting with the dissolved monomer molecules. However, after adding a few monomer units in the chains, these chains no longer remain water soluble and come out of the solution. These chains are not stable on their own and keep collapsing with each other in order to attain stability. They also adsorb a certain amount of surfactant from either the micelles or the aqueous phase itself. Partial stability is also provided by the negative charges from the initiator moieties. In the case of the surfactant-free poly­mer­i­za­tion, the initiator charges are the only source of colloidal stability of the particles. Figure 1.2b shows the process of homogenous nucleation. The emulsion poly­mer­i­za­tion process is generally divided into three intervals. The first is the particle formation interval. The radicals are generated in the aqueous phase after the thermal dissociation of the initiator. These radicals start entering the micelles and initiate poly­mer­i­za­tion. These active micelles where the poly­mer­i­za­tion starts to take place are then referred to as poly­mer particles. The number of particles in this interval keeps increasing owing to the continuous entry of the generated radicals in the micelles. This also leads to continuous increase in the rate of the poly­mer­i­za­tion. As the poly­ mer­i­za­tion of the monomer in the particles proceeds, the size of the particles keeps increasing and the amount of monomer in the particles keeps depleting. However, this depletion of the monomer is replenished by the absorption of

Polymer Latex Technology: An Overview

5

(a)

(b) Figure 1.2 (a) Representation of micellar nucleation mechanism for the generation of poly­mer particles. (b) Homogenous nucleation mechanism for the synthesis of poly­mer particles.

the monomer from the aqueous phase. The aqueous phase in turn absorbs more monomer from the monomer droplets. Therefore, a mass transfer from the monomer droplets to the poly­mer articles keeps taking place during the course of poly­mer­i­za­tion. For this diffusion process to take place, the monomer is required to be partially soluble in water. As the poly­mer particles become bigger in size and their surface area increases as a function of time or

6

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Figure 1.3 Schematic of various intervals of the emulsion poly­mer­i­za­t ion process.

monomer conversion, they require more amount of surfactant to remain stable. The surfactant dissolved in the aqueous phase is continuously adsorbed on the surface of the poly­mer particles, leading to the reduction of the surfactant amount in the solution to lower than the critical micelle concentration. This in turn destabilizes the remaining micelles and these micelles disappear, providing their surfactant for the stabilization of the poly­mer particles. Thus at the end of the first interval, no micelle is left and most of the surfactant is used to stabilize the poly­mer particles. It has to be noted that the final number of poly­mer particles is much lower than the original number of micelles. Also, roughly 15% of the monomer is poly­mer­ized by the end of the first interval [1]. Figure 1.3 represents the various intervals of emulsion poly­mer­i­za­tion. Once excess surfactant is no longer present in the system, no new particles nucleate. This marks the beginning of the second interval of emulsion poly­mer­i ­za­t ion. Because no new particles nucleate, the amount of the particles remains almost constant; this also leads to an almost constant poly­mer­i ­za­t ion rate in this interval. The size of the poly­mer particles, however, keeps increasing as a function of conversion. The monomer present in the monomer droplets continues to replenish the monomer in the aqueous phase as well as monomer-swollen poly­mer particles. After a certain extent of conversion, the monomer droplets also disappear. This also signals the start of the final interval of the emulsion poly­mer­i ­za­ tion process. The concentration of the monomer in the poly­mer particles keeps decreasing, and as a result the rate of poly­mer­i ­za­t ion also steadily decreases. Because the monomer is almost consumed, the poly­mer­i ­za­t ion rate virtually falls to zero. Figure 1.4 shows the evolution of the particle size as a function of conversion.

7

Polymer Latex Technology: An Overview

300 nm

200 nm (a)

(b)

400 nm (c) Figure 1.4 (a–c) Increase of the size of the particles as a function of conversion.

Emulsion poly­mer­i­za­tion can also lead to the generation of various different surface morphologies of the poly­mer particles as well as particle sizes or families. Figure 1.5 shows the examples of monomodal, bimodal, or multimodal poly­mer particles along with morphologies like planar, orange-peel, strawberry or surface craters, etc. Polymers synthesized with emulsion poly­mer­i­za­tion are not always homopolymers, but most of the time are copolymers. When more than one monomer is poly­mer­ized together, the reactivity of the monomers defines the resulting morphology of the particles. Different reactivities of the monomer lead to totally different copolymer composition in the poly­mer particles, leading to a gradient in the concentration of the monomers with radius. This occurs because of the faster poly­mer­i­za­tion of the reactive monomer thus accumulating near the center of the particles, followed by the poly­mer­i­za­tion of the lesser reactive monomer, which then is present in a majority near the

8

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

300 nm

200 nm (a)

(b)

250 nm (c)

300 nm (d)

Figure 1.5 (a–d) Various morphologies of particles achieved with emulsion poly­mer­i­za­t ion.

outer surface of the particles. Differences in the water solubilities of the monomers can also lead to the generation of specific morphologies of the particles. As an example, in Figure 1.6 are shown the copolymer particles of styreneco-N-isopropylacrylamide synthesized by the surfactant-free approach, that is, by the homogenous nucleation method. N-isopropylacrylamide being hydrophilic in nature starts to poly­mer­ize first, followed by the poly­mer­i­ za­tion of more hydrophobic styrene. But because the poly­mer chains from styrene are also hydrophobic in nature, they push the hydrophilic chains of poly(N-isopropylacrylamide) away to the surface, leading to the morphology as shown in Figure 1.6.

9

Polymer Latex Technology: An Overview

300 nm

250 nm

(a)

(b)

300 nm (c) Figure 1.6 (a–c) Scanning electron microscopy (SEM) micrographs of copolymer particles of styrene-coN-isopropylacrylamide.

1.3 Controlled Polymerization and its Use in Emulsion Polymerization Processes The conventional radical poly­mer­i­za­tion is limited as a technique in that the control in the molecular weight or its distribution is difficult to achieve. It is also not easy to achieve well-defined morphologies in the particles like block copolymers because the life of the radical is too short, and uncontrolled termination reactions take place very fast. Controlled living poly­mer­i­za­tion techniques, on the other hand, can circumvent the aforementioned limitations in the emulsion poly­mer­i­za­tion process [4]. In these techniques, the chains

10

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

TEMPO mediated nitroxide polymerization (NMP) Atom transfer radical polymerization (ATRP)

Activator regenerated by elecron transfer (ARGET) atom transfer radical polymerization (ATRP)

SG1 mediated nitroxide polymerization (NMP) Degenerative transfer

Living polymerization

Activator generated by elecron transfer (AGET) atom transfer radical polymerization (ATRP)

Reversible additionfragmentation chain transfer (RAFT) polymerization

Reverse atom transfer radical polymerization (ATRP)

Figure 1.7 Representation of various living poly­mer­i­za­t ion techniques. (Reprinted from V. Mittal, Advances in Polymer Latex Technology, New York: Nova Science Publishers, 2009. With permission.)

are terminated but only irreversibly, and after a short period of time become active again to propagate the poly­mer chains. In such processes, the termination reactions are effectively eliminated, and the controlled molecular weight distributions as well as advanced morphologies in the poly­mer particles can be achieved. There have been many techniques developed in the last years to achieve controlled poly­mer­i­za­tion, and these techniques are generally classified into two categories: those based on reversible termination and those based on reversible transfer. Figure 1.7 is the representation of the various controlled poly­mer­i­za­tion techniques. In the category of reversible termination, nitroxide-mediated poly­mer­i­za­tion (NMP) and atom transfer radical poly­mer­i­za­tion (ATRP) are the most studied approaches. ATRP has also been further modified into techniques like reverse atom transfer radical poly­mer­ i­za­tion, activator generated by electron transfer ATRP, etc. In the category of reversible transfer, techniques like reversible addition-­fragmentation chain transfer (RAFT) poly­mer­i­za­tion and degenerative transfer are mostly reported. During the poly­mer­i­za­tion, the concentration of dormant species continues to increase as compared to the active chains. At the end of poly­ mer­i­za­tion, the dormant species may be present in amounts six times higher than the active chains. This effectively leads to elimination of termination and allows much longer lifetimes for the radicals.

Polymer Latex Technology: An Overview

11

NMP, where nitroxides are used to irreversibly terminate the poly­mer chains, has been used in two different ways. In one case, a conventional free radical initiator and a separately added nitroxide are added to control the poly­mer­i­za­tion. The two most commonly used nitroxides for this purpose are 2,2,6,6-tetramethyl-1-piperidinoxyl (TEMPO) and N-ter-butyl-1diethylphosphono-2,2’-dimethylpropyl (SG1). The nitroxides were initially developed for the poly­mer­i­za­tion of styrene; however, a number of other nitroxides have been developed that are also suitable for the poly­mer­i­za­tion of acrylates. In the other case, an alkoxyamine is used, the decomposition of which leads to the generation of two radicals: one reactive and one stable. This radical pair then controls the poly­mer­i­za­tion and thus does not require the addition of conventional free radical initiator. Figures 1.8 and 1.9 represent the poly­mer­i­za­tion of lauryl methacrylate and styrene by using nitroxides and alkoxyamines, respectively. The only disadvantage of the nitroxide-mediated stable free radical poly­mer­i­za­tion was the requirement of a high temperature for the poly­mer­i­za­tion reaction, which is sometimes not feasible for thermally sensitive systems; however, various nitroxides have been developed that also allow use at lower reaction temperatures. The initially carried-out reactions with styrene in emulsion led to poor colloidal stability, which resulted in a large amount of coagulum generated in the poly­mer­i­za­tion reactions. It was claimed that the particle nucleation as well as poly­mer­i­za­tion in droplets were a few reasons, among others, for this behavior. The seed method has also been described for emulsion poly­mer­ i­za­tion with SG1 as nitroxide [7]. In this case, a seed is generated first with low solid content, and the seed particles are then swollen in monomer and followed by subsequent poly­mer­i­za­tion of these seed particles. This helps to avoid the generation of monomer droplets and thus poly­mer­i­za­tion in droplets. It was also possible to achieve the previously described reaction as a single step. After the synthesis of seed as before, a certain amount of monomer is added without cooling the seed latex and the reaction is run until high conversion is achieved. The formed latexes were very stable in nature and no coagulum was generated. It is also important to monitor the progress of the reaction especially at high conversion, as at very high conversions, chains start to terminate each other and the polydispersity in the chain length as well as molecular weight increases. Therefore, it is always beneficial to stop the poly­mer­i­za­tion reaction a little below the full conversion. It was also confirmed that the alkoxyamines based on SG1 are more optimally operatable for achieving controlled poly­mer­i­za­tion of a wide range of monomers as compared to TEMPO nitroxide. ATRP represents another technique based on the principle of reversible termination, and in this process, an organic halide is used to irreversibly terminate the propagating chains. This technique has been very successful for the controlled poly­mer­i­za­tion of styrenics as well as acrylates and methacrylates. It also does not require very high temperatures as compared

12

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

O C

CH2

O O

O

CH C

+

C

O

OC12H25

O C

CH2

O

CH C

• CH

CH2 O

C

OC12H25

CH2

CH

+

O

O

C

OC12H25

OC12H25

CH3 H3C •O

OC2H5

CH3 N

CH

H3C

P CH3

OC2H5 O

CH3 CH3

O C

H3C O

CH2

CH C

CH2 O

OC12H25

CH C

O O

OC12H25

CH3 N

CH

H3C

OC2H5 P CH3

OC2H5 O

CH3

Figure 1.8 Nitroxide-mediated controlled radical poly­mer­i­za­t ion of lauryl methacrylate with SG1 nitroxide.

to NMP, and in many cases can also be undertaken at room temperature. Figure 1.10a shows the schematic of the ATRP process. Cuprous salt forms a complex with ligand, L (amines of different chemical architectures), which makes it more soluble in the solvents [1]. Initiation of the reaction takes place by the dissociation of the halide atom from the initiator and leading to the generation of a free reactive radical. The bromide atom is captured by cuprous halide ligand complex and it forms CuBr2 ligand complex. This compound is very stable and hence is called deactivator. The generation of this compound thus leads to reduction in the concentration of the free radical species in the system. The growing radical continues to add monomer units to the poly­mer chain, and at some point it comes in contact with CuBr2

13

Polymer Latex Technology: An Overview

CH H3C

H3C

• CH

• CH

N

O

• O

+

H3C

CH3

CH2

CH3

H3C

CH3

H3C

N H3C CH3

CH

+

CH2

CH

H3C

CH

H3C

H3C • O

CH3

N H3C CH3

CH3

H3C CH

CH2

CH

N

O

H3C

H3C

CH2

CH3

CH

n H3C CH H3C

CH2

CH

CH2 n

CH

O

CH3

N H3C

CH3

Figure 1.9 Nitroxide-mediated free radical poly­mer­i­za­t ion of styrene by using alkoxyamine as nitroxide as well as initiator.

ligand complex and is temporarily terminated by the formation of RMn+1-Br compound. It is also possible to carry out the reverse ATRP process similarly (Figure 1.10b). In this process, a conventional free radical initiator like AIBN or benzoyl peroxide is used to initiate the poly­mer­i­za­tion reaction, which is controlled by the addition of CuBr2 ligand complex. The radicals add few monomer units, and during this process come in contact with this complex to form the dormant species. One limitation of such a technique is the presence of transition metal in the final particles, which though possible to wash off adds another processing step in the synthesis process. Another limitation

14

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

P

P• +

Br + CuBr/L

CuBr2/L

M PM• nM PM•n+1

RMn+1 – Br +

CuBr/L

(a) O C

O

O O

O

+

C

CuBr2/L

C

O

Br

M O C

O

M•

nM

O C

O

M•n+1

+

CuBr2/L

O C

O

M•n+1

Br

+

CuBr/L

(b) Figure 1.10 Schematic of (a) ATRP and (b) reverse ATRP processes for controlled living poly­mer­i­za­t ion. (Adapted from G. Odian, Principles of Polymerization, Hoboken, NJ: John Wiley & Sons, 2004; and V. Mittal, Advances in Polymer Latex Technology, New York: Nova Science Publishers, 2009.)

is the reaction of the copper compounds with the other constituents of the system. One example is the reaction of these compounds with the emulsifier used in the poly­mer­i­za­tion system, leading to the poisoning of the initiator, which subsequently results in no or little poly­mer­i­za­tion. Therefore, it is possible to work in the emulsion with the ATRP when there is no surfactant or surfactants with no interaction with the initiator are chosen. ATRP in emulsion processes also faced problems similar to those in NMP. In one reported study, ethyl 2-bromoisobutyrate was used as an ATRP initiator, and copper bromide was complexed with 4,4’-dinonyl-2,2’-bipyridyl to form the catalyst system [8]. Nonionic surfactant Tween 85 was used. The poly­mer­i­za­tion was achieved by first mixing together copper salts with 4,4’-dinonyl-2,2’-bipyridyl, to which the monomer was added. The solution was allowed to mix and was added with surfactant. To this solution, water was added under vigorous

15

Polymer Latex Technology: An Overview

stirring to form the emulsion. To this emulsion was then added the initiator to initiate the poly­mer­i­za­tion reaction. The reaction conditions needed to be very accurately controlled, and the reaction was overall very sensitive to minor changes in the reaction parameters. Seeded poly­mer­i­za­tion similar to that used with NMP was also used in this case. The use of cationic surfactants was also reported for the ATRP processes in emulsion. Dodecyl trimethyl ammonium bromide and myristyl trimethyl ammonium bromide were used as cationic surfactants, and their effect on the latex stability, amount of coagulum, and the polydispersity in the molecular weight was quantified. The first surfactant though gave a good control of polydispersity; however, the whole system was observed to coagulate after the initiation of poly­mer­i­ za­tion. In the case of the second surfactant, the latex stability was better, but the polydispersity in the molecular weight or chain lengths was very high. RAFT is a controlled poly­mer­i­za­tion technique based on the principle of reversible transfer. The core of this process is a RAFT agent that contains dithioester groups. The living poly­mer­i­za­tion takes place because the transferred end group in the polymeric dithioester is as labile as the dithioester group in the starting RAFT agent. The initiator for the poly­mer­i­za­tion can be the conventional initiators like AIBN or benzoyl peroxide. Figure  1.11 explains the principle of RAFT poly­mer­i­za­tion. Though it is one of the versatile techniques for the poly­mer­i­za­tion of a large number of monomers, it also has its own limitations, such as the presence of remainder RAFT agent and the commercial unavailability of the RAFT agents. Similar to NMP and ATRP, initial trials with RAFT also were faced with difficulties of coagulum generation. The RAFT agent was difficult to be transported to the poly­ mer particles through the aqueous phase. RAFT poly­mer­i­za­tion of styrene in emulsion was reported by Szkurhan et al. [9]. The process named nano­ precipitation was carried out by forming nano-sized particles by precipitation of the acetone solution of macro RAFT agent in the aqueous poly(vinyl alcohol) solution. The macro RAFT agent was prepared by conventional free R1

Mn + S

SR2

MnS

R1

M•m + S

R1

R1 •

SR2

MmS

•

S

MnS R1

R1 SMn

+ R•2

SMn

MmS

+ M•n S

Figure 1.11 Mechanism of reversible transfer processes used in reversible addition-fragmentation chain transfer processes. (Adapted from G. Odian, Principles of Polymerization, Hoboken, NJ: John Wiley & Sons, 2004; and V. Mittal, Advances in Polymer Latex Technology, New York: Nova Science Publishers, 2009.)

16

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

radical poly­mer­i­za­tion. The formed nanoparticles were subsequently swollen with monomer and were poly­mer­ized in the living manner. This nanoprecipitation method was also named seeded poly­mer­i­za­tion because, in this case, the nano-sized particles formed by precipitation act as seeds to form poly­mer particles. Both water- and oil-soluble initiators were used. When the initiator used was oil soluble, it was premixed with the RAFT agent, whereas the water-soluble initiator was dissolved in PVA solution. With both watersoluble and oil-soluble initiators, the rate of poly­mer­i­za­tion was quite slow, and increasing the reaction temperature was not helpful in increasing the rate of poly­mer­i­za­tion. Another study reported the synthesis of poly­mer particles in emulsion by RAFT without the problems of loss of colloidal stability and the molecular weight control [10]. Trithiocarbonate RAFT agents were used in the study to form short stabilizing blocks from a hydrophilic monomer, from which diblocks were created by the subsequent poly­mer­ i­za­tion of a hydrophobic monomer. These diblocks self-assembled to form micelles, and subsequent poly­mer­i­za­tion could be carried out. Figure  1.12 demonstrates the particles generated by this technique.

1.4 Conventional and Controlled Miniemulsion Polymerization In surfactant-aided emulsion poly­mer­i­za­tion, the goal is to achieve the micellar nucleation and to avoid the droplet nucleation as much as possible. But the poly­mer­i­za­tion of extremely hydrophobic monomers by conventional emulsion poly­mer­i­za­tion is not possible because of their inability to diffuse from the monomer droplets through the aqueous phase to the poly­mer particles. To achieve poly­mer­i­za­tion of such systems, miniemulsion poly­mer­i­za­tion has proved to be a versatile method [2,3]. The mode of poly­mer­i­za­tion is based on the droplet poly­mer­i­za­tion principle. The monomer droplets are generated by shearing the system with high energy along with the addition of costabilizer (with the surfactant), which needs to be hydrophobic in order to avoid the collapse of the monomer droplets by Ostwald ripening when the shearing of the system is stopped. Thus in this mode of poly­mer­i­za­tion, it is important to avoid the micellar nucleation; therefore, the amount of surfactant is below the critical micelle concentration. The particles in the general size range of 50–500 nm can be synthesized by using miniemulsion poly­mer­i­za­tion. These are similar in size to the monomer droplets in the beginning of the poly­mer­ i­za­tion. The initiators used for the poly­mer­i­za­tion are water soluble as in the case of emulsion poly­mer­i­za­tion. The initiator on dissociation generates radicals in the aqueous phase, and these radicals enter the droplets and initiate poly­mer­i­za­tion. In conventional emulsion poly­mer­i­za­tion, also called macroemulsion poly­mer­i­za­tion, the micellar nucleation is very sensitive and is affected by a large number of factors like surfactant amount, initiator amount,

17

Polymer Latex Technology: An Overview

Conventional core-shell: different chains in the core and shell

Triblock polymer: the same chains extend from the shell into the core (a)

0.20 µm X 19000

(b) Figure 1.12 (a) Schematic representation of RAFT-based triblock copolymer chains forming the core and shell of the particles and their comparison with conventional core-shell particles. (b) TEM micrograph of poly(acrylic acid)-b-poly(butyl acrylate)-b-polystyrene particles. (Reprinted from C. J. Ferguson, R. J. Hughes, D. Nguyen, T. T. Pham, R. G. Gilbert, A. K. Serelis, C. H. Such, and B. S. Hawkett, Macromolecules 38: 2191–2204, 2005. With permission from the American Chemical Society.)

18

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Figure 1.13 Schematic of the miniemulsion poly­mer­i­za­t ion process. The molecules with black and gray color represent the surfactant and costabilizer, respectively.

agitation, reaction temperature, etc. However, that is not the case in miniemulsion poly­mer­i­za­tion. Figure 1.13 also represents the scheme of poly­mer­i­za­tion in miniemulsion. The monomer is added to the surfactant and costabilizer in the aqueous phase followed by homogenization under high shear to break the bigger monomer droplets into droplets with the size range of 10–500 nm [2,3,11]. The amount of the surfactants and the shearing translate into the size of the monomer droplets. As mentioned earlier, in emulsion poly­mer­i­za­tion, the poly­mer­i­za­tion is driven by the diffusion of the monomer through the aqueous phase. In this process, monomer droplets disappear and the micelles convert into the poly­mer particles, whereas in miniemulsion poly­mer­i­za­tion, the monomer droplets directly translate into poly­mer particles. As a result, the rate of poly­mer­i­za­tion is also different for these two processes. The rate of poly­mer­i­za­tion in the emulsion poly­mer­i­za­tion first increases owing to the generation of the particles and reaches a constant phase after the disappearance of the micelles. The rate then decreases owing to the depletion of the monomer in the particles. As there is no diffusion of monomer in the miniemulsion poly­mer­i­za­tion, the constant rate period is absent. The rate first increases owing to the nucleation of the particles and then decreases when the monomer is consumed in the particles. Not only hydrophobic monomers, but also extremely hydrophilic monomers can be poly­mer­ized using the miniemulsion poly­mer­i­za­tion method. In this case, one has to use the inverse miniemulsion poly­mer­i­za­tion. Also in this case, hydrophobic reaction medium is used along with a lipophobe used as costabilizer. One must be clear that the addition of costabilizer stops the conversion of a miniemulsion into a conventional emulsion; however, the addition of a costabilizer to conventional emulsion does not automatically convert it into a miniemulsion. It is only after the addition of high shearing energy that it becomes a stable miniemulsion. The costabilizers should be hydrophobic, soluble in monomer, and have a low molecular weight. However, the use of conventional costabilizers like cetyl alcohol and hexadecane pose a potential hazard owing to their volatility, and the presence of these even in the minor amounts in the poly­mer particles may not be acceptable for many applications. Therefore, a lot of research effort has been focused in the direction of generation of more compatible costabilizers. Polymeric stabilizers from the poly­mer of the monomer

Polymer Latex Technology: An Overview

19

to be poly­mer­ized have been used in some of the reported studies [3,12,13]. These polymers are soluble in their own monomers and thus allow better intermixing at the interphase. They also eliminate the use of volatile costabilizers, providing more acceptability to the system for the commercial applications. Monomeric costabilizers have also been developed in recent years that can copoly­mer­ize with the monomer under poly­mer­i­za­tion [14]. These costabilizers form copolymer chains that are bound inside the particles, and thus the possibility of the diffusion of low molecular weight components out of the particles is eliminated. The potential diffusion of the low molecular weight components, especially substances like cetyl alcohol or hexadecane, can pose health hazards when the poly­mer particles are used in application with food contact. Similarly, the other components of the poly­mer­i­za­tion system like initiator and chain transfer agent have also been used as costabilizers [15,16]. Therefore, the materials act as dual-role components. They not only perform their function as initiator or chain transfer agent, respectively, but also help to achieve the stability for the monomer droplets and poly­mer particles. Miniemulsion poly­mer­i­za­tion has also been proved to be advantageous in living poly­mer­i­za­tion systems. The various living poly­mer­i­za­tion methods like NMP, ATRP, and RAFT have been shown to be beneficial in miniemulsion poly­mer­i­za­tion to generate specialty polymers or polymers with special architecture like block copolymers. Colloidal stability and ease of poly­mer­ i­za­tion process are also better in the case of miniemulsion poly­mer­i­za­tion than conventional emulsion poly­mer­i­za­tion. For NMP, nitroxide-capped poly­mer chains have been used as initiator as well as nitroxide. The use of such nitroxide-capped poly­mer chains for the initiation and reaction control allows one to properly estimate the number of starting chains in the system, helping to achieve better control of the molecular weight. The use of nitroxide-capped poly­mer also helps to partition the nitroxide solely in the organic phase owing to the hydrophobicity. In such reported studies with polystyrene terminated with TEMPO as initiator as well as nitroxide, hexadecane as costabilizer, and DOWFAX 8390 as surfactant, it was reported that changing the amount of surfactant led to the generation of different particle sizes, but the rate of poly­mer­i­za­tion was not affected, which is different from the behavior seen in conventional emulsion poly­mer­i­za­tion [17,18]. Figure 1.14 demonstrates the transmission electron microscopy (TEM) images of the polystyrene particles generated in nitroxide-mediated miniemulsion poly­mer­i­za­tion using different amounts of TEMPO-terminated oligomers of polystyrene as macroinitiator. A great deal of process development has been reported for ATRP in miniemulsion. A number of studies have been reported that apply the direct or forward ATRP in miniemulsion, but reverse ATRP, in which conventional free radical poly­mer­i­za­tion initiator like AIBN can be used with the transition metal compound in its higher oxidation state, was observed to be more suitable for miniemulsion poly­mer­i­za­tion. This eliminates the use of air-sensitive Cu(I) species and requires only the use of Cu(II) species, which

20

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

(a)

(b)

Figure 1.14 TEM images of the polystyrene particles prepared by nitroxide-mediated miniemulsion poly­ mer­i­za­t ion using different amounts of TEMPO-terminated oligomers of polystyrene (TTOPS) as macroinitiator. (a) 5% TTOPS and (b) 20% TTOPS (100 nm). (Reprinted from G. Pan, E. D. Sudol, V. L. Dimonie, and M. S. El-Aasser, Macromolecules 34: 481–88, 2001. With permission from the American Chemical Society.)

is more stable in air. A narrow molecular weight distribution as well as linear increase in the molecular weight as a function of conversion was reported, and the final latexes were stable over a period of time. In one such study on reverse ATRP processes [19], Brij 98 surfactant and CuBr2/dNbpy (4,4’-di[5nonyl]-4,4’-bipyridine) complex were used along with hexadecane costabilizer. Both water-soluble as well as oil-soluble initiators were used for the poly­mer­i­za­tion. It was observed that the poly­mer­i­za­tion rate was independent of the size and number of particles and the amount of surfactant. The shear forces were able to influence only the size of the particles and not the poly­mer­i­za­tion rate. In the case of oil-soluble initiator, the poly­mer­i­za­tion was observed to proceed by droplet nucleation mode because the monomersoluble initiator was already present in the droplet during the miniemulsion; whereas when water-soluble initiator was used, both micellar as well as droplet nucleation were reported to take place. Similarly RAFT has also been used successfully in miniemulsion for the poly­mer­i­za­tion of styrene as well as water-soluble monomers like acrylamide [11,20–22].

1.5 Generation of Copolymer or Core-Shell Particles The generation of well-defined copolymer morphologies like block copoly­mer particles is difficult to achieve by the use of conventional emulsion poly­mer­ i­za­tion because of the uncontrolled free radical poly­mer­i­za­tion and the short life of the radicals. To achieve certain control on the copoly­mer­i­za­tion, monomer reactivity ratios and monomer-feeding methodology must be considered.

21

Polymer Latex Technology: An Overview

300 nm

300 nm

(a)

(b)

300 nm

300 nm (c)

(d)

Figure 1.15 (a–d) Different morphologies of copolymer particles generated by conventional emulsion poly­ mer­i­za­t ion.

The monomers have different reactivity ratios; therefore, if the monomers are added together, the more reactive monomer starts to poly­mer­ize first followed by the poly­mer­i­za­tion of the less reactive monomer. This creates a gradient of concentration of the monomer units in the poly­mer particles as a function of radius. Figure 1.15 provides some examples of various copolymer particles that can be achieved by emulsion poly­mer­i­za­tion like core-shell grafted particles, core-shell particles with hydrophilic shell and hydrophobic core, copolymer particles with different surface morphologies, etc. Apart from reactivity ratios, mode of addition of the monomers during the course of poly­mer­i­za­tion is also of utmost importance to achieve control on the particle characteristics. Batch addition of the monomers does not lead to generation of the structured latexes; therefore, semibatch addition of the monomers is generally preferred. This mode of addition can be achieved by either flooded

22

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

addition or starved addition of the monomers. In flooded addition, monomers are added at a rate higher than their rate of consumption. This mode of addition leads to buildup of the monomers in the poly­mer­i­za­tion reaction and may lead to the generation of secondary nucleation of the particles. Starved addition of the monomers, on the other hand, is the addition of monomers at a rate slower than their poly­mer­i­za­tion rate, and this allows one to retain the chemical composition of the poly­mer chains equal to the monomer ratios in the feed or according to the requirement. The starved conditions eliminate the possibility of secondary nucleation, though one has to be careful about the control of the amount of the surfactant in the system as well as charges on the surface. As an example, if copoly­mer­i­za­tion of a hydrophilic monomer and a hydrophobic monomer is considered, initially the surface may be hydrophobic, but as the chains rich in hydrophilic monomer content get pushed out to the surface of the particles during the course of poly­mer­i­za­tion, the surface becomes hydrophilic. This would lead to a change in the surface properties of the particles and would allow the release of the surfactant from the surface of the particles owing to the hydrophili­city. This also results in the nonentry of the hydrophobic monomer into the poly­mer particles, causing monomer concentration drift in particles or secondary nucleation. Interesting studies have been reported for the generation of copolymer particle latexes by emulsion poly­mer­i­za­tion. Batch poly­mer­i­za­tion of copoly­mer particles of polystyrene and poly(methyl methacrylate) were reported without the use of initiators [23]. These copolymer particles of poly(methyl methacrylateco-styrene) were prepared by thermally initiated emulsion copoly­mer­i­za­tion. It was observed that totally different particle morphologies like hemispherical, sandwich-like, core-shell, inverted core-shell particle morphologies, etc. were obtained depending on the poly­mer­i­za­tion conditions. It was reported that the incorporation of the initiator fragments to one end of the chains allows the polystyrene chains to become more hydrophilic, changing the surface nature of the poly­mer particles. In another study to generate copolymer particles, poly(methyl methacrylate) seed was used to generate the copolymer particles of poly(methyl methacrylate) with polystyrene [24]. It was observed that by using the oil-soluble initiators, an inverted core-shell morphology of the particles was obtained, in which the polystyrene chains were present in the core of the particles and the poly(methyl methacrylate) covered the particles owing to its hydrophilicity. In the case of water-soluble initiator, the morphology was less affected by the hydrophilicity of the polymers, but was more affected by the initiator concentration and poly­mer­i­za­tion temperature. Controlled living poly­mer­i­za­tion methods provide much better possibilities to generate the structured latex particles with different morphologies of chemistries owing to the prolonging of the radical age either by reversible termination or by reversible transfer. In one such study to generate triblock copolymers using emulsion poly­mer­i­za­tion, water-soluble SG1based bifunctional alkoxyamine (Figure  1.16; sodium salt of alkoxyamine was used owing to water solubility) and Dowfax 8390 surfactant were used

23

Polymer Latex Technology: An Overview

HOOC

O N

O P O O

O CH2 CH2 O 3

O

O

t-butanol T = 80 – 100°C

HOOC

O O P

COOH O CH2 CH2 O

N O

O N

3

O

O

O

O (1) NaOH (2)

R

R = Ph, COOBu

Emulsion T = 112°C

COO– +Na

Na+ –OOC R O O P O

N O

O P O

R O CH2 CH2 O

x

3

O

O

x

O N

O P O O

Figure 1.16 Synthesis and use of SG1-based water-soluble bifunctional alkoxyamine. (Reprinted from J. Nicolas, B. Charleux, O. Guerret, and S. Magnet, Macromolecules 38: 9963–73, 2005. With permission from the American Chemical Society.)

[11,25]. When a bifunctional alkoxyamine was used, two functional ends of this alkoxyamine could be used to generate triblock copolymers. Thus, in order to generate polystyrene-b-poly(butyl acrylate)-b-polystyrene triblock copolymer particles, a seed was first generated from butyl acrylate particles. The seed was further swollen with butyl acrylate to form central poly(butyl acrylate) block in the emulsion particles. The particles were then added with styrene to form two blocks of styrene around the central poly(butyl acrylate) block to form the triblock copolymer. In another study using ATRP, the seeded-poly­mer­i­za­tion approach was used to synthesize block copolymers of poly(i-butyl methacrylate) and polystyrene using ethyl 2-bromoisobutyrate as initiator and CuBr/4,4’-dinonyl-2,2’-dipyridinyl as catalyst ligand

24

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

800 nm

300 nm (a)

(b)

100 nm (c)

250 nm (d)

Figure 1.17 (a, b) SEM and TEM micrographs of latex particles functionalized with an ATRP initiator. (c, d) The grafted brushes of thermally responsive poly­mer poly(N-isopropylacrylamide) from the surface of the ATRP initiator functionalized particles.

complex [26]. Tween 80 (polyoxyethylene sorbitan monooleate) was used as surfactant. First a seed of poly(i-butyl methacrylate) end-capped with ATRP initiator was prepared to which a batch of styrene then was added to form a block copolymer. Thermally responsive poly­mer particles were also reported by the use of ATRP [27–29]. The process included the synthesis of seed particles, functionalization of seed particles by ATRP initiator, and the grafting of the poly(N-isopropylacrylamide) chains from the surface. Figure 1.17 shows these functional particles [28]. In another study using RAFT poly­mer­i­za­ tion, core-shell functional particles were achieved by using o-­ethylxanthyl

Polymer Latex Technology: An Overview

25

pTA/RuO4 cryo

Observation at –150°C

Figure 1.18 Core-shell particles of polystyrene-b-poly(butyl acrylate)/poly(acetoacetoxy ethyl methacrylate). The black core represents polystyrene whereas the soft shell is poly(butyl acrylate)/ poly(acetoacetoxy ethyl methacrylate) component. (Reprinted from M. J. Monteiro and J. de Barbeyrac, Macromolecules 34: 4416–23, 2001. With permission from the American Chemical Society.)

ethyl propionate as RAFT agent [30]. The poly­mer­i­za­tion reactions were carried out in the presence of poly(methyl methacrylate) seed particles of predetermined number and size distribution. The seed was added first with styrene monomer to form polystyrene block, which was then added with butyl acrylate. Styrene was added in batch conditions, whereas butyl acrylate was added slowly to the emulsion system so as to avoid the buildup of high concentration of monomer in this system. Similarly, core-shell particles consisting of block copolymer of polystyrene-b-poly/butyl acrylate)/ poly(acetoacetoxy ethyl methacrylate) were also prepared by using xanthates as RAFT agents. Figure  1.18 shows the TEM image of such core-shell particles [31]. Miniemulsion poly­mer­i­za­tion has also been extensively used for the synthesis of functional latex particles [32–38].

References

1. Odian, G. 2004. Principles of poly­mer­iz­ a­tion. Hoboken, NJ: John Wiley & Sons. 2. Landfester, K. 2001. Polyreactions in miniemulsions. Macromolecular Rapid Communications 22:896–936.

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

3. Schork, F. J., Luo, Y., Smulders, W., Russum, J. P., Butté, A., and K. Fontenot. 2005. Miniemulsion poly­mer­i­za­tion. Advances in Polymer Science 175:129–255. 4. Matyjaszewski, K., and T. P. Davis. 2002. Handbook of radical poly­mer­i­za­tion. Hoboken, NJ: John Wiley & Sons. 5. Hiemenz, P. C., and R. Rajagopalan. 1997. Principles of colloid and surface chemis­ try. New York: Marcel Dekker. 6. Mittal, V. 2009. Advances in poly­mer latex technology. New York: Nova Science Publishers. 7. Nicolas, J., Charleux, B., and S. Magnet. 2006. Multistep and semibatch nitroxide-mediated controlled free-radical emulsion poly­mer­i­za­tion: A significant step toward conceivable industrial processes. Journal of Polymer Science, Part A: Polymer Chemistry 44:4142–53. 8. Eslami, H., and S. Zhu. 2005. Emulsion atom transfer radical poly­mer­i­za­tion of 2-ethylhexyl methacrylate. Polymer 46:5484–93. 9. Szkurhan, A. R., Kasahara, T., and M. K. Georges. 2006. Reversible-addition fragmentation chain transfer radical emulsion poly­mer­i­za­tion by a nanoprecipitation process. Journal of Polymer Science, Part A: Polymer Chemistry 44:5708–18. 10. Ferguson, C. J., Hughes, R. J., Nguyen, D., Pham, B. T. T., Gilbert, R. G., Serelis, A. K., Such, C. H., and B. S. Hawkett. 2005. Ab initio emulsion poly­mer­iz­ a­tion by RAFT-controlled self-assembly. Macromolecules 38:2191–2204. 11. Cunningham, M. F. 2008. Controlled/living radical poly­mer­i­za­tion in aqueous dispersed systems. Progress in Polymer Science 33:365–98. 12. Reimers, J. L., and F. J. Schork. 1996. Predominant droplet nucleation in emulsion poly­mer­i­za­tion. Journal of Applied Polymer Science 60:251–62. 13. Reimers, J., and F. J. Schork. 1996. Robust nucleation in poly­mer-stabilized miniemulsion poly­mer­iz­ a­tion. Journal of Applied Polymer Science 59:1833–41. 14. Reimers, J. L., and F. J. Schork. 1996. Miniemulsion copoly­mer­i­za­tion using water-insoluble comonomers as cosurfactants. Polymer Reaction Engineering 4:135–52. 15. Reimers, J. L., and F. J. Schork. 1997. Lauroyl peroxide as cosurfactant in miniemulsion poly­mer­i­za­tion. Industrial Engineering Research 36:1085–87. 16. Mouran, D., Reimers, J., and F. J. Schork. 1996. Miniemulsion poly­mer­iz­ a­tion of methyl methacrylate with dodecyl mercaptan as cosurfactant. Journal of Polymer Science, Part A: Polymer Chemistry 34:1073–81. 17. Pan, G., Sudol, E. D., Dimonie, V. L., and M. S. El-Aasser. 2002. Surfactant concentration effects on nitroxide-mediated living free radical miniemulsion poly­ mer­i­za­tion of styrene. Macromolecules 35:6915–19. 18. Pan, G., Sudol, E. D., Dimonie, V. L., and M. S. El-Aasser. 2001. Nitroxide-mediated living free radical miniemulsion poly­mer­i­za­tion of styrene. Macromolecules 34:481–88. 19. Matyajaszewski, K., Qiu, J., Tsarevsky, N. V., and B. Charleux. 2000. Atom transfer radical poly­mer­iz­ a­tion of n-butyl methacrylate in an aqueous dispersed system: A miniemulsion approach. Journal of Polymer Science, Part A: Polymer Chemistry 38:4724–34. 20. Moad, G., Chiefari, J., Chong, Y. K., Krstina, J., Mayadunne, R. T. A., Postma, A., Rizzardo, E., and S. H. Thang. 2002. Living free radical poly­mer­i­za­tion with reversible addition-fragmentation chain transfer (the life of RAFT). Polymer International 49:993–1001.

Polymer Latex Technology: An Overview

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21. Butté, A., Storti, G., and M. Morbidelli. 2001. Miniemulsion living free radical poly­mer­i­za­tion by RAFT. Macromolecules 34:5885–96. 22. Qi, G., Jones, C. W., and F. J. Schork. 2007. RAFT inverse miniemulsion poly­mer­ i­za­tion of acrylamide. Macromolecular Rapid Communications 28:1010–16. 23. Du, Y. Z., Ma, G. H., Ni, H. M., Nagai, M., and S. Omi. 2002. Morphological studies in thermally initiated emulsion (co)poly­mer­i­za­tion without conventional initiators. Journal of Applied Polymer Science 84:1737–48. 24. Cho, I., and K. W. Lee. 1985. Morphology of latex particles formed by poly(methyl methacrylate)-seeded emulsion poly­mer­i­za­tion of styrene. Journal of Applied Polymer Science 30:1903–26. 25. Nicolas, J., Charleux, B., Guerret, O., and S. Magnet. 2005. Nitroxide-mediated controlled free-radical emulsion poly­mer­i­za­tion using a difunctional water­soluble alkoxyamine initiator. Toward the control of particle size, particle size distribution, and the synthesis of triblock copolymers. Macromolecules 38:9963–73. 26. Okubo, M., Minami, H., and J. Zhou. 2004. Preparation of block copolymer by atom transfer radical seeded emulsion poly­mer­i­za­tion. Colloid and Polymer Science 282:747–52. 27. Mittal, V., Matsko, N. B., Butté, A., and M. Morbidelli. 2007. Functionalized polystyrene latex particles as substrates for ATRP: Surface and colloidal characterization. Polymer 48:2806–17. 28. Mittal, V., Matsko, N. B., Butté, A., and M. Morbidelli. 2007. Synthesis of temperature responsive poly­mer brushes from polystyrene latex particles functionalized with ATRP initiator. European Polymer Journal 43:4868–81. 29. Mittal, V., Matsko, N. B., Butté, A., and M. Morbidelli. 2008. Swelling deswelling behavior of PS-PNIPAAM copolymer particles and PNIPAAM brushes grafted from polystyrene particles & monoliths. Macromolecular Materials and Engineering 293:491–502. 30. Smulders, W., and M. J. Monteiro. 2004. Seeded emulsion poly­mer­i­za­tion of block copolymer core-shell nanoparticles with controlled particle size and molecular weight distribution using xanthate-based RAFT poly­mer­i­za­tion. Macromolecules 37:4474–83. 31. Monteiro, M. J., and J. de Barbeyrac. 2001. Free-radical poly­mer­i­za­tion of styrene in emulsion using a reversible addition-fragmentation chain transfer agent with a low transfer constant: Effect on rate, particle size, and molecular weight. Macromolecules 34:4416–23. 32. Farcet, C., and B. Charleux. 2002. Nitroxide-mediated miniemulsion poly­mer­i­ za­tion of n-butyl acrylate: Synthesis of controlled homopolymers and gradient copolymers with styrene. Macromolecular Symposia 182:249–60. 33. Tortosa, K., Smith, J.-A., and M. F. Cunningham. 2001. Synthesis of ­polystyrene-block-poly(butyl acrylate) copolymers using nitroxide-­mediated living radical poly­mer­i­za­tion in miniemulsion. Macromolecular Rapid Commun­ ications 22:957–61. 34. Keoshkerian, B., MacLeod, P. J., and M. K. Georges. 2001. Block copolymer synthesis by a miniemulsion stable free radical poly­mer­i­za­tion process. Macromolecules 34:3594–99. 35. Li, M., Jahed, N. M., Min, K., and K. Matyjaszewski. 2004. Preparation of linear and star-shaped block copolymers by ATRP using simultaneous reverse and normal initiation process in bulk and miniemulsion. Macromolecules 37:2434–41.

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36. Min, K., Li, M., and K. Matyjaszewski. 2005. Preparation of gradient copolymers via ATRP using a simultaneous reverse and normal initiation process. I. Spontaneous gradient. Journal of Polymer Science, Part A: Polymer Chemistry 43:3616–22. 37. Min, K., Gao, H., and K. Matyjaszewski. 2005. Preparation of homopolymers and block copolymers in miniemulsion by ATRP using activators generated by electron transfer (AGET). Journal of the American Chemical Society 127:3825–30. 38. Luo, Y., and X. Liu. 2004. Reversible addition-fragmentation transfer (RAFT) copoly­mer­i­za­tion of methyl methacrylate and styrene in miniemulsion. Journal of Polymer Science, Part A: Polymer Chemistry 42:6248–58.

2 Synthesis of Polymer Particles with Core-Shell Morphologies Claudia Sayer and Pedro Henrique Hermes de Araújo Contents 2.1 Introduction................................................................................................... 29 2.2 Equilibrium and Nonequilibrium Morphologies....................................30 2.2.1 Equilibrium Morphologies.............................................................. 31 2.2.2 Nonequilibrium Morphologies....................................................... 33 2.3 Synthesis of Core-Shell Particles................................................................ 35 2.3.1 Emulsion Polymerization................................................................ 35 2.3.1.1 Synthesis of Core-Shell Particles (CS)............................. 37 2.3.1.2 Synthesis of Inverted Core-Shell Particles (ICS)............ 41 2.3.2 Miniemulsion Polymerization........................................................43 2.3.3 Microemulsion Polymerization...................................................... 47 2.3.4 Dispersion Polymerization.............................................................. 47 2.3.5 Suspension Polymerization............................................................. 48 2.3.6 Other Techniques.............................................................................. 49 2.4 Characterization of Core-Shell Particles.................................................... 52 2.4.1 Transmission Electron Microscopy................................................ 52 2.4.2 Scanning Electron Microscopy.......................................................54 2.4.3 Atomic Force Microscopy................................................................54 2.4.4 Additional Techniques Used for Particle Characterization........54 References................................................................................................................ 55

2.1 Introduction Core-shell poly­mer particles have received a great deal of industrial and academic interest in the last decades. These multicomponent particles with controlled morphology create a versatile class of materials in which the final properties depend not only on the composition of each poly­mer phase but also on the morphology of these particles. This characteristic opens the

29

30

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

­ ossibility for tailor-made properties for each application as, for instance, p soft core–hard shell results in particles suitable to act as impact modifiers, and hard core–soft shell latex particles result in paints with low film formation temperature. In addition, via core-shell poly­mer­i­za­tion, it is also possible to get incompatible polymers into one particle or to add functionality either into the core or into the shell (Koskinen and Wilén 2009). Structured particles can be obtained with different morphologies: welldefined core-shell structure, inverted core-shell, interface with a gradient of both core and shell, interface with microclusters, and multiple or irregularly shaped shells (Sundberg and Durant 2003). The final morphology depends on both thermodynamic and kinetic aspects, as quite frequently the equilibrium morphology may not be achieved due to kinetic control of the morphology development. The poly­mer­i ­za­t ion techniques play a major role in the particle size as well as in the kinetic control of the poly­mer­i ­za­t ion. Several heterogeneous poly­mer­i ­za­t ion techniques such as emulsion, miniemulsion, microemulsion, dispersion, and suspension ­poly­mer­i ­za­t ions could be employed to obtain poly­mer particles with core-shell structures. The first three techniques lead to the formation of submicrometric particles (10–800  nm), whereas the two last are used, respectively, to prepare small (1–30  µm) and large (50–1500  µm) micro­metric particles. The end use properties of the structured particles depend on the design and control of particle morphology; therefore, it is necessary to understand how this morphology can be controlled and which are the main features of each poly­mer­i ­za­t ion technique related to particle morphology control. The purpose of this chapter is to describe the factors that will lead to a certain particle morphology and to discuss the heterogeneous poly­mer­i­za­ tion techniques that could be employed to obtain those particles. Section 2.2 introduces the basics of equilibrium and nonequilibrium morphologies. Section 2.3 deals with the different heterogeneous poly­mer­i­za­tion techniques and the main features related to morphology control. Section 2.4 discusses briefly the characterization techniques, as any work in this area relies on the need to adequately characterize particle morphology.

2.2 Equilibrium and Nonequilibrium Morphologies The formation of core-shell particles is a challenging issue of poly­mer reaction engineering in dispersed media. In principle, the most stable particle morphology is determined by thermodynamics according to the minimum interfacial energy (González-Ortiz and Asua 1995), as given by Equation (2.1):

31

Synthesis of Polymer Particles with Core-Shell Morphologies



1 φ= 2

3

3

∑∑ a σ ij

ij



(2.1)

i=1 j=1 j≠i

where aij and σij are, respectively, the interfacial area and the interfacial tension between phases i and j. Nevertheless, frequently the equilibrium morphology is not achieved since particle morphology depends on the interplay between thermodynamics, which establishes the equilibrium morphology, and kinetics. If kinetic control prevails, nonequilibrium-type (metastable or kinetically stable) structures may be formed. In the following paragraphs, equilibrium morphologies and the main factors that establish these morphologies will be discussed, followed by nonequilibrium ones. 2.2.1 Equilibrium Morphologies Figure  2.1 shows four different equilibrium morphologies for a two­component system based on the poly­mer-poly­mer and poly­mer-aqueous phase interfacial tensions, which determine the interfacial energy and, consequently, also the equilibrium morphology for a given system. The equilibrium morphologies are: • Core-shell (CS), in which the second-stage poly­mer 2 (●) forms a continuous shell around the seed poly­mer 1 (○) dispersed in the aqueous phase 3. This equilibrium morphology might be achieved when either (a) poly­mer 1 is more hydrophobic than poly­mer 2 (σ13 > σ23) and poly­mer 2 has more affinity with poly­mer 1 than with the aqueous phase (σ12 < σ23) or (b) poly­mer 1 has more affinity with poly­mer 2 than with the aqueous phase (σ12 < σ13) and poly­mer 2 has less affinity with poly­mer 1 than with the aqueous phase (σ12 > σ23). • Inverted core-shell (ICS), in which the seed poly­mer 1 forms a continuous shell around the second-stage poly­mer 2. This equilibrium morphology might be obtained when poly­mer 2 is more hydrophobic than poly­mer 1 (σ23 > σ13) and poly­mer 2 has more affinity with poly­ mer 1 than with the aqueous phase (σ12 < σ23). • Hemisphere, snowman-like, Janus, half-moon, occluded, partially engulfed, depending on the different degrees of protrusion and on the different curvatures of the poly­mer/poly­mer interface and the coverage of one poly­mer upon the other (Sundberg and Durant 2003). This equilibrium morphology might be achieved under different conditions: (a) when poly­mer 2 has similar affinities with poly­mer 1 and with the aqueous phase (σ12 ≈ σ23); (b) when poly­mer 2 has more



◉

○●

32

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

(σ23 – σ12) σ13

10

1

0.1 0.1

1

σ12 σ23

10

Figure 2.1 Equilibrium morphologies for a two-component system: ○ poly­mer 1 (seed), ● poly­mer 2 (produced by the poly­mer­i­za­t ion of the second-stage monomer). σ12: interfacial tension between polymers 1 and 2; σ13: interfacial tension between poly­mer 1 and aqueous phase; σ23: interfacial tension between poly­mer 2 and aqueous phase. (Reprinted from V. Herrera, R. Pirri, J. R. Leiza, and J. M. Asua, Macromolecules 39: 6969–74, 2006. With permission.)

○●

affinity with poly­mer 1 than with the aqueous phase (σ12 < σ23) and both polymers have similar affinities with the aqueous phase (ǀσ23 – σ12ǀ ≤ σ13); (c) when poly­mer 2 has less affinity with poly­mer 1 than with the aqueous phase (σ12 > σ23) and poly­mer 1 has similar affinities with poly­mer 2 and the aqueous phase (ǀσ23 – σ12ǀ ≤ σ13). • Separate particles of the different polymers. This equilibrium morphology might be obtained when both polymers have more affinity with the aqueous phase than with each other (σ13 < σ12) and (σ23 < σ12). As shown in Figure  2.1, equilibrium morphologies of two-component systems are established basically by three interfacial tension values. Notwithstanding, several factors influence these three interfacial tensions and may, therefore, be used for particle morphology control purposes. Besides poly­mer types, which determine the interfacial tension between the polymers and affect the interfacial tension between each poly­mer and the aqueous phase, poly­mer-poly­mer interfacial tension can be influenced substantially by compatibilizing agents, and the interfacial tensions between each poly­mer and the aqueous phase are also affected by the types and amounts of surfactant and initiator. In addition, it has been shown that the equilibrium morphology may also be affected by the level of cross-linking of poly­mer 1, which influences the free energy (Sundberg and Durant 2003), and by the molecular weights of the polymers, since the interfacial tension between the poly­mer phases, which is much lower than that between the poly­mer and the aqueous phase, depends on the molecular weight (Tanaka

Synthesis of Polymer Particles with Core-Shell Morphologies

33

et al. 2008). Finally, the ratio between polymers 1 and 2 may affect the curvature of the poly­mer-poly­mer interface in the hemisphere morphology (Sundberg and Durant 2003), and the CS and ICS morphologies may not be achieved if the amount of the shell forming poly­mer (poly­mer 2) in CS and poly­mer 1 in ICS is not enough to form a continuous shell with a minimum thickness. If copolymers are to be considered, the analysis becomes more complex since the surface and interfacial tensions depend on the copolymer compositions. 2.2.2 Nonequilibrium Morphologies As mentioned at the beginning of this section, quite frequently the equilibrium morphology is not achieved due to kinetic control of the morphology development. In this case, nonequilibrium-type structures may be formed. Three main processes have been used by González-Ortiz and Asua (1995, 1996a, 1996b) to describe the morphology development:

1. The formation of poly­mer chains occurs at a given position in the poly­mer particle.



2. Incompatible poly­mer chains cause phase separation leading to the formation of clusters.



3. Clusters migrate toward the equilibrium morphology in order to minimize the Gibbs free energy. During this migration the size of the clusters may increase by (i) poly­mer­i­za­tion of monomer inside the cluster, (ii) diffusion of poly­mer chains into the cluster, and (iii) coagulation with other clusters. The rates of process (ii) and (iii) depend strongly on the particle viscosity.

The Sundberg group has studied the effect of several factors on the morphology development during two-stage emulsion poly­mer­i­za­tions, especially those involving the less hydrophobic copolymer of methyl methacrylate and methyl acrylate as seed poly­mer and polystyrene as the more hydrophobic second-stage poly­mer. Durant et al. (1997) verified the influence of different amounts of cross-linking monomer (EGDMA) during the syntheses of the PMMA cores on the morphology of PMMA/PS particles. It was observed that 0.015  wt% EGDMA was enough to shift the particle morphology from ICS (second-stage PS in the core) toward CS. At 0.2 wt% EGDMA, the particles was essentially of the CS morphology. Cross-linking during the second stage, on the other hand, was observed by Stubbs and Sundberg (2006) to have very little, if any, effect on morphology, though it enhances the mechanical stability of the shell. The effect of the feed rate of the second-stage more hydrophobic monomer (styrene) when less hydrophobic high-Tg seed polymers (poly[methyl methacrylate]) are used was studied by Stubbs et al. (1999). Fast second-stage monomer addition resulted in CS

34

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

particles, whereas slower addition increased the number of occlusions of the hydrophobic second-stage poly­mer. When less hydrophobic low-Tg seed poly­ mer (poly[methyl acrylate]) was used, ICS was obtained independently of the second-stage monomer feed rate. Ivarsson et al. (2000) and Karlsson et al. (2003) verified that it is possible to keep the more hydrophobic second-stage poly­mer (styrene) at the shell of the particles if the reaction temperature is less than 15°C above Tg of the seed copolymer (poly[methyl methacrylate]/ poly[methyl acrylate]). Stubbs and Sundberg (2004) observed that, though ionic initiators that are able to anchor the chains of the second-stage poly­mer to the particle surface make it more likely to obtain CS morphologies with poly(methyl methacrylate)/poly(methyl acrylate) core and polystyrene shell under some conditions, this effect is not dominant under most conditions. Based on these results, Stubbs and Sundberg (2008) proposed the decision flowchart shown in Figure 2.2 to be used for morphology prediction of latex particles obtained by emulsion poly­mer­i­za­tion. Stubbs and Sundberg (2008) considered three main questions for the prediction of the morphology of composite particles: the first one is whether radicals may penetrate during the second stage of the synthesis, the second is about phase separation, and the last is related to phase consolidation. The theory of radical penetration considers that in emulsion poly­mer­i­za­tion, radicals are typically created in the water phase, and thus enter latex particles at the outer particle surface.

1

Penetration possible?

Yes No

Yes Phase separation possible? Yes Phase consolidation possible? Yes Extent large or small?

No

2

σ13 > σ23 No

4 No

Core-shell

Gradient or mixed phase Small occlusions

Yes

Tg2 < Treaction No

Core-shell 3

5

Small

Large occlusions

Large

Equilibrium morphology

Lobed particle

6 7

Figure 2.2 Adaptation of the decision tree flowchart for predicting morphology development in multiphase particles proposed by Stubbs and Sundberg (2008). σ13: interfacial tension between poly­ mer 1 and aqueous phase; σ23: interfacial tension between poly­mer 2 and aqueous phase; Tg2: glass transition temperature of poly­mer 2. (Reprinted from J. M. Stubbs and D. C. Sundberg, Progress in Organic Coatings 61: 156–65, 2008. With permission.).

Synthesis of Polymer Particles with Core-Shell Morphologies

35

The extent of radical penetration will depend on the effective Tg of the seed poly­mer. The effective Tg considers that the particle will be partially swollen with second-stage monomer during the poly­mer­i­za­tion and this will lower its glass transition temperature below that of the pure poly­mer. When penetration is possible, a second-stage poly­mer chain will find itself inside the particle and fully entangled with the seed poly­mer chains. Phase separation then requires chain diffusion in order to get multiple chains together, and this process may be so slow that phase separation is not possible. The driving force for morphology rearrangement is the minimization of interfacial free energy, and the system will evolve toward the equilibrium morphology if given sufficient time. However, the process of phase consolidation requires an increased extent of poly­mer mobility compared to the previous two processes of oligomeric radical penetration and poly­mer phase separation.

2.3 Synthesis of Core-Shell Particles Particles with core-shell morphologies may be synthesized by a number of heterogeneous poly­mer­i­za­tion techniques such as emulsion, miniemulsion, microemulsion, dispersion, and suspension poly­mer­i­za­tions. The first three techniques lead to the formation of submicrometric particles (10–800  nm), whereas the two last are used, respectively, to prepare small (1–30 µm) and large (50–1500  µm) micrometric particles. Nevertheless, it must be kept in mind that in any of these techniques, the application of a two-stage strategy to build up a shell of the second-stage poly­mer onto the core of the first-stage poly­mer core will not necessarily lead to the formation of particles with coreshell morphology (Rajatapiti et al. 1997). In the next sections, the synthesis of particles with core-shell structure by these different techniques will be described. A detailed description of these poly­mer­i­za­tion techniques can be found in several excellent books involving emulsion poly­mer­i­za­tion (Piirma 1982; Gilbert 1995; Lovell and El-Aasser 1997; Van Herk 2005), as well as in recent book chapters about emulsion (de la Cal et al. 2005; Nomura et al. 2005), miniemulsion (Schork et al. 2005), microemulsion (Chow and Gan 2005), dispersion (Kawagushi and Ito 2005), suspension (Brooks 2005), and heterogeneous (Van Herk and Monteiro 2002) poly­mer­i­za­tion techniques. 2.3.1 Emulsion Polymerization Emulsion poly­mer­i­za­tion is a heterogeneous poly­mer­i­za­tion system composed of water, an initiator (usually water soluble), surfactant (usually above the critical micelle concentration [CMC]), and monomer with low water solubility, which under stirring forms droplets with diameters ranging from 1 to

36

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

10  µm. The main locus of poly­mer­i­za­tion is not in these monomer droplets, but within the submicrometric monomer-swollen poly­mer particles (60–800 nm). In ab initio emulsion poly­mer­i­za­tions, these poly­mer particles are formed at the beginning of the poly­mer­i­za­tion by the entry of radicals into micelles, if the surfactant concentration is above the CMC (micellar nucleation mechanism) and/or by the precipitation of growing oligomers in the aqueous phase (homogeneous nucleation mechanism). Due to the relatively large size of the monomer droplets compared to the size of monomer-swollen micelles (10–20 nm), the surface area of the monomer droplets is orders of magnitude smaller than that of the micelles and, consequently, the radical entry into monomer droplets (droplet nucleation) is insignificant. Since monomer droplet nucleation is insignificant and monomer-swollen poly­mer particles, instead of monomer droplets, are the main poly­mer­i­za­tion locus, monomer droplets act as monomer reservoirs and the monomer must be transported from these droplets by diffusion through the aqueous phase to allow the growth of the poly­mer particles by poly­mer­i­za­tion. In seeded emulsion poly­mer­i­za­tions, poly­mer particles (seeds) are added at the beginning of the poly­mer­i­za­tion and, usually, these reactions are conducted in the absence of micelles to avoid secondary particle nucleation. Seeded emulsion poly­mer­i­za­tion is by far the most applied technique for the synthesis of structured poly­mer particles with core-shell morphology. And two operation modes, batch and semicontinuous, with or without preswelling of the seed particles, are commonly used in these seeded emulsion poly­mer­i­ za­tions. When direct CS particles with a first-stage poly­mer core and a secondstage poly­mer shell are to be obtained, usually the second-stage monomer is continuously fed at a prespecified rate in order to allow the second-stage poly­mer to build up upon the surface of the seed particles, forming a uniform and continuous shell. In this case, reaction conditions that avoid or minimize phase consolidation are often required, especially in those cases in which the CS morphology is not the equilibrium morphology. When, on the other hand, ICS particles with a second-stage poly­mer core and a first-stage poly­mer shell are to be obtained, usually seed particles are swelled by the second-stage monomer prior to either batch or flooded semicontinuous poly­mer­i­za­tion of the second monomer, since conditions that allow phase consolidation are required for phase inversion leading to the equilibrium ICS morphology. The choice of the best operation mode relies strongly on the poly­mer types and whether the core-shell morphology is to be achieved directly (CS) or through phase inversion (ICS). In the following, the syntheses of CS and ICS particles via emulsion poly­ mer­i­za­tion will be discussed. This also includes some works in which the first-stage poly­mer seeds were synthesized via miniemulsion poly­mer­i­ za­tion and the second-stage monomer poly­mer­i­za­tion was performed via emulsion poly­mer­i­za­tion.

Synthesis of Polymer Particles with Core-Shell Morphologies

37

2.3.1.1 Synthesis of Core-Shell Particles (CS) In this strategy the second-stage poly­mer should build up upon the surface of the seed particles, forming a uniform and continuous and, consequently, concentric shell. As a consequence, CS particles may be formed independently of this being the equilibrium morphology. If CS is not the equilibrium morphology, reaction conditions must be carefully adjusted to avoid and/or minimize phase consolidation. Several conditions may favor the formation of CS particles: • High superficial area of the first-stage poly­mer. This can be achieved by using small seed particles and/or high seed contents. • Reaction temperature below or close to the glass transition temperature of the poly­mer particles. If the Tg of the seed poly­mer is not too low, this might be achieved by starved second-stage monomer feed and/or high initiation rate to keep second-stage monomer concentration, and its plasticizing effect, low in the particles. • Cross-linked core poly­mer to reduce diffusion of the second-stage monomer and, especially, of the radicals into seed particles. • Enhanced hydrophobicity of seed poly­mer through its synthesis using an oil-soluble initiator and/or copoly­mer­i­za­tion with a hydrophobic monomer. • Aqueous phase initiator that is able to anchor the second-stage radicals at the particle surface. • If the incompatibility between the first- and second-stage polymers is too high to allow the formation of particles with a CS structure, the use of a compatibilizing agent is advised to reduce the poly­mer-­poly­ mer interfacial tension. This compatibilizing agent can be produced in situ by the incorporation of a proper macromonomer (Nelliappan et al. 1996), comonomer (Sherman and Ford 2005), or CRP agent (Herrera et al. 2006) during the synthesis of the seed poly­mer. Though this strategy might seem the most straightforward for the synthesis of CS particles with hydrophobic cores and hydrophilic shells, in some cases it may result in considerable secondary nucleation instead of the formation of CS particles, since several points listed previously, as for instance high aqueous phase initiator concentration, may lead to homogenous particle nucleation. A quite complete study was presented by Ferguson et al. (2002), who succeeded in synthesizing PS/PVAc core-shell latexes with small cores. In this case the small size of the PS seed particles (unswollen diameter of 88 nm) resulted in a high enough superficial area to capture PVAc radicals formed in the aqueous phase. When, on the other hand, PS seed particles with unswollen diameter of 400 nm were used, excessive new particle formation occurred and

38

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

no PVAc shells could be detected. Numerous strategies for overcoming this were evaluated through simulations with a simplified nucleation model and/or implemented experimentally, as for instance using an organic-phase initiator in the seeded poly­mer­i­za­tion to avoid homogeneous nucleation or addition of surfactant during the seeded poly­mer­i­za­tion in order to maintain the surface charge density and keep the surfactant concentration below the CMC, but always either extensive secondary nucleation occurred or the system became colloidally unstable. Similar results were obtained by Sherman and Ford (2005). The authors used a cross-linked 80/20 PS/PMMA seed 70 nm in diameter to form cationic PS/PMMA CS particles with acentric cores with 530 nm in three steps of PMMA growth, using starved semicontinuous addition of MMA to avoid secondary nucleation and a single initial addition of aqueous phase initiator to provide fast radical generation. The increase of the diameter of the core latex, on the other hand, led to secondary particle nucleation. Due to the incompatibility of PS and PMMA, the equilibrium morphology of the PS/PMMA system is as a double-ball structure. Consequently, when PS homopolymer seeds are used without any procedure to reduce the interfacial tension between both polymers, the CS morphology usually is not attained. A good illustration of the effect of the operation mode on the morphology of PS/PMMA particles was shown in the work of Jönssin et al. (1991). On one extreme, in the seeded batch poly­mer­i­za­tion of MMA, the authors observed the formation of composite particles with large cluster sizes. Whereas when the seeded semicontinuous poly­mer­i­za­tion of MMA was conducted under starved conditions, composite particles with small cluster sizes were formed. Both reduction of particle viscosity and the rate of initiation lead to structures with increased cluster sizes. Postpoly­mer­i­za­tion treatment with solvents leads to the equilibrium morphology (double-ball). In a recent study, Jönssin et al. (2007) verified the morphology of PMMA (first-stage)/PS (second-stage) particles prepared by semicontinuous seeded emulsion poly­mer­i­za­tion of styrene in the presence of polar PMMA seed particles, using different conditions of nonpolar styrene feed rate, radical formation rate, seed particle concentration, and temperature of poly­mer­i­za­tion. The authors observed that, depending on the set of process conditions used, the morphology of the resulting two-phase particles varied from that of a PMMA/PS CS structure, over intermediate structures in which a shell of PS surrounded a PMMA core containing an increasing number of PS clusters, to a structure in which the entire PS phase was present as discrete PS phase clusters, more or less evenly distributed in a matrix of PMMA. Figure 2.3 (a–d) shows transmission electron microscopy (TEM) micrographs of the microtomed sections of samples of reactions A, B, and C conducted with the same formulation and under the same conditions except for the second-monomer (styrene) feed rate, which was increased from A to C and of reaction D, carried out with the same formulation and conditions of reaction C, but with a higher initiator (KPS) feed rate. The higher the feed rate of the second monomer, the higher is its plasticizing effect and the lower is the Tg of the poly­mer

Synthesis of Polymer Particles with Core-Shell Morphologies

(a)

(b)

(c)

(d)

39

Figure 2.3 (a–d) TEM micrographs of thin sections taken from particles obtained in experiments A–D. (e) Rate of poly­mer­i­za­t ion for experiments A–D. (f) The amount of styrene accumulated in the reactor as calculated from the poly­mer­i­za­t ion curves from experiments A–D, F, and G. (Reprinted from J.-E. L. Jönsson, O. L. Karlsson, H. Hassander, and B. Törnell, European Polymer Journal 43: 1322–32, 2007. With permission.)

40

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Rate of Polymerization (W)

1.2 D

1

C

0.8

B

0.6

A

0.4 0.2 0

0

100

200

300 400 Time (min.) (e)

500

600

Accumulated Styrene (g/g)

0.25 C

0.2 0.15

G

0.1 0.05 0

B

D

A F

0

100

200

300 400 Time (min.) (f )

500

600

Figure 2.3 (continued).

particles; consequently, the higher becomes the diffusivity of the entering oligo radicals, increasing the number and distributing more homogeneously the PS clusters in the PMMA matrix. Results of reaction D, conducted with the same styrene feed rate as reaction C, but with a higher initiator feed rate, indicate the formation of a direct CS structure; this is attributed to the high reaction rate (Figure 2.3e), leading to low monomer concentrations in the poly­mer particles (Figure  2.3f) and, consequently, increasing the Tg of the poly­mer particles to only a few degrees below the reaction temperature. Consequently, contrary to the expected equilibrium morphologies, twophase particles with a true core-shell structure were obtained in experiments where the estimated glass transition temperature of the PMMA phase was only a few degrees below the poly­mer­i­za­tion temperature, independently

Synthesis of Polymer Particles with Core-Shell Morphologies

41

of the feed rate of the second monomer, provided that the rate of initiation, using an aqueous phase initiator, was properly adjusted. The formation of particles with nonequilibrium morphologies was also observed by Zhao et al. (2004), who studied the morphological development of PVAc (first-stage)/PBuA (second-stage) in seeded semicontinuous starved emulsion poly­mer­i­za­t ion using an aqueous phase initiator in the synthesis of both seed and second-stage poly­mer. The authors observed that, despite the low Tgs of both seed and second-stage polymers, the PBuA was formed at the outside of the PVAc seed. After storage for 1.5 years at room temperature, latex morphology evolved to the equilibrium morphology, which for this system is ICS with PBuA core and a PVAc (more hydrophilic) shell. 2.3.1.2 Synthesis of Inverted Core-Shell Particles (ICS) As mentioned in the previous section (2.3.1.1), sometimes the synthesis of structured poly­mer particle presenting the core-shell morphology may be very difficult, either because the CS morphology is not favored thermodynamically or because secondary particle nucleation is difficult to avoid. Often in these cases, the synthesis of ICS particles formed by a core of the secondstage poly­mer and a shell of first-stage poly­mer is an alternative that should not be discarded. For the synthesis of inverted core-shell particles, conditions must be carefully chosen to favor phase inversion. Consequently, contrary to CS particles, ICS particles may be formed only if this is the equilibrium morphology. Several conditions may favor the formation of ICS particles: • High superficial area of the first-stage poly­mer to avoid secondary particle nucleation. This can be achieved by using small seed particles and/or high seed contents. • Reaction temperature much above (Ivarsson et al. 2000; Karlsson et al. 2003) glass transition temperature of the poly­mer particles. This might be achieved by either batch or flooded semicontinuous second-stage poly­mer­i­za­tion with preswelling and/or low initiation rate to keep second-stage monomer concentration, and its plasticizing effect, high in the particles. • Chain transfer agent (CTA) to reduce the molecular weight of the polymers. • Enhanced hydrophilicity of seed poly­mer through its synthesis using an aqueous phase initiator and/or copoly­mer­i­za­tion with a hydrophilic monomer. • Enhanced hydrophobicity of the second-stage poly­mer through its synthesis using an oil-soluble initiator that is not able to anchor the second-stage radicals at the particle surface.

42

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

• If the incompatibility between the first- and second-stage polymers is too high to allow the formation of particles with an ICS structure, the use of a compatibilizing agent is advised to reduce the ­poly­mer-­poly­mer interfacial tension. This compatibilizing agent can be produced in situ by the incorporation of a proper macromonomer (Nelliappan et al. 1996), comonomer (Sherman and Ford 2005), or CRP agent (Herrera et al. 2006) during the synthesis of the seed poly­mer. Most of the factors just listed were mentioned by Lee and Ishikawa (1983), who found that when hydrophobic monomers are poly­mer­ized in the presence of highly hydrophilic poly­mer seed particles, the second-stage hydrophobic polymers form cores surrounded by the first-stage hydrophilic polymers, resulting in inverted core-shell latexes. They also observed that the formation of the core-shell morphology by this inversion process is favored by higher hydrophilicity, lower interfacial tension, lower molecular weight of hydrophilic first-stage poly­mer, and greater phase separation between both polymers, which is expected to increase with greater incompatibility between these polymers, lower glass transition temperatures of both polymers, lower molecular weights and cross-linking, higher poly­ mer­i­za­tion temperatures, and more flooded conditions. In the case of the soft poly­mer pair systems, the formation of inverted core-shell morphology was equally complete, regardless of the molecular weight of the hydrophilic poly­mer molecules, whereas in the case of the hard poly­mer pair systems, the efficiency of inversion was dependent on the molecular weights of both hydrophilic and hydrophobic polymers. In the work of Ferguson et al. (2002), the synthesis of PS(first stage)/ PVAc(second stage) core-shell particles with large cores was hampered by secondary nucleation. Nevertheless, in a different attempt, Ferguson et al. (2003) showed that it is possible to synthesize PS/PVAc core-shell particles with large PS cores through an inverse core-shell synthesis using PVAc seed particles in a batch styrene poly­mer­i­za­tion. For this system, the inverse coreshell morphology is favored thermodynamically, and undesired secondary particle nucleation is avoided by the low aqueous phase solubility of styrene. Nevertheless, the authors observed that conditions had to be chosen carefully in order to minimize the kinetic control on the morphology, allowing the achievement of the ICS morphology. To keep it short, the fast diffusion of the hydrophilic seed poly­mer had to be ensured, for instance by using a chain transfer agent (to reduce the molecular weight and, especially, the degree of branching), an initiator able to minimize grafting between both polymers, and a comonomer in the seed poly­mer to increase its hydrophilicity. An important aspect of ICS syntheses mentioned in this work is that even for those systems in which the ICS is thermodynamically favored and kinetically achievable, there is no driving force for this core to be concentric

Synthesis of Polymer Particles with Core-Shell Morphologies

43

100 nm

100 nm 100 nm (a) Latex 1 (with SG1)

(b) Latex 2 (without SG1)

(c) Latex 3 (with CTA)

Figure 2.4 TEM micrographs of PS/PMMA composite particles stained with PTA and RuO4. (Reprinted from V. Herrera, R. Pirri, J. R. Leiza, and J. M. Asua, Macromolecules 39: 6969–74, 2006. With permission.).

in an ICS latex (as long as the hydrophobic core is shielded from the particlewater interface region). The high incompatibility of the poly­mer phases may be overcome by the incorporation of a compatibilizing agent. Herrera et al. (2006) added during the miniemulsion poly­mer­i­za­tion for the formation of the PMMA seed a small amount of a CRP agent, so that at the end of the seed formation some of the poly­mer chains were capped with the CRP agent. Batch emulsion poly­mer­i­za­tion of the second-stage monomer (styrene, with previous swelling) in the presence of additional initiator led to the in situ formation of block copolymer chains. When PMMA seeds were synthesized in the presence of the CRP agent, ICS structures were formed (Figure  2.4a). On the other hand, in similar reactions with PMMA seeds synthesized without CRP agent, the hemisphere morphology was obtained, independently of the molecular weight of the seed PMMA poly­mer (PMMA seeds formed without, Figure  2.4b, or with chain transfer agent, Figure  2.4c). This result indicated that the in situ formation of block copolymer chains allowed the modification of particle morphology through the reduction of the interfacial tension between the two polymers, helping to increase their compatibility and, consequently, allowing the formation of the ICS morphology. 2.3.2 Miniemulsion Polymerization Miniemulsion poly­mer­i­za­tion differs from a conventional emulsion poly­ mer­i­za­tion in that the monomer droplets, formed with the aid of highshear devices (rotor-stator system, sonifier, high-pressure homogenizer), are in a submicrometric range (50–500 nm) forming a miniemulsion that is

44

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

thermodynamically unstable, but kinetically metastable (stable for a period ranging from hours to months) due to the addition of a surfactant to minimize coalescence and a costabilizer to retard droplet diffusion degradation (Ostwald ripening). Free surfactant concentrations in the aqueous phase are usually kept below the CMC, and the relatively small size of the monomer droplets favors droplet nucleation. Thus, droplet nucleation and poly­mer­ i­za­tion within the submicrometric miniemulsion droplets are aimed in a miniemulsion poly­mer­i­za­tion. Either oil- or water-soluble initiators may be used. In miniemulsion poly­mer­i­za­tion, the first-stage poly­mer may be dissolved in the second-stage monomer, and this solution, with or without the addition of a costabilizer, is dispersed in the aqueous phase containing a surfactant using an adequate homogenization equipment; the formed miniemulsion of submicrometric organic phase droplets is subsequently poly­mer­ized, maximizing droplet nucleation. This approach has the advantage that the firststage poly­mer must not be in the form of nanoparticles, being well suited for the synthesis of hybrid poly­mer particles composed of a poly­mer produced by step-growth poly­mer­i­za­tion and a poly­mer produced by free radical poly­ mer­i­za­tion (Wang et al. 1996; Wu et al. 1999; Barrere and Landfester 2003; Li et al. 2005; Wang et al. 2005; Guyot et al. 2007; Jahanzad et al. 2007). The drawback of this approach is that the amount of first-stage poly­mer is limited by the viscosity increase of the organic phase, which depends strongly on the molecular weight of the first-stage poly­mer. However, this amount can reach up to 50 wt% related to the organic phase as shown by López et al. (2008), who succeeded in preparing miniemulsions with droplet sizes around 100 nm using first-stage polymers (alkyd resins and poly[ε-caprolactone]) dissolved in acrylic monomers. It has also been shown that hybrid poly­ mer particles may also be synthesized by simultaneous poly­mer­i­za­tion in miniemulsion, as in Barrere and Landfester (2003), who synthesized hybrid polystyrene/polyurethane and poly(butyl acrylate)/polyurethane particles via miniemulsion poly­mer­i­za­tion by combining polyaddition and radical poly­mer­i­za­tion. The hybrid particles obtained by miniemulsion poly­mer­i­za­tion will show only CS or ICS structures if these are the equilibrium morphologies and if they are kinetically achievable. This is the case of the work of Rodríguez et al. (2008), where it was shown that most particles obtained by silicon-acrylic miniemulsion poly­mer­i­za­tion presented nonreactive polydimethyl­siloxane divinyl terminated (PDMS)-rich core morphologies, as PDMS is highly hydrophobic. In the case of the ICS structures, the ratio (first-stage poly­ mer):(second-stage monomer) must be high enough to allow the formation of a continuous shell. An increasing number of publications involve the synthesis via miniemulsion poly­mer­i­za­tion of CS particles with a liquid core (nanocapsules). The procedure is quite the same as for the synthesis of hybrid particles using a

Synthesis of Polymer Particles with Core-Shell Morphologies

45

100 nm (a) Figure 2.5 (a) TEM micrograph of PS (styrene poly­mer­ized with 10 wt% acrylic acid) nanocapsules with hexadecane core in a 1:1 (PS:HD) ratio prepared by miniemulsion poly­mer­i­za­t ion. (Reprinted from K. Tiarks, K. Landfester, and M. Antonietti, Langmuir 17: 908–18, 2006. With permission.) (b) TEM and SEM (insert) micrographs of PMMA nanocapsules with Neobee M-5 core in a 1:1 (PMMA:Neobee M5) ratio obtained by miniemulsion poly­mer­i­za­t ion. Arrows with indexes TEC, PEC, and NEC indicate, respectively, totally engulfing capsules, partially engulfing capsules, and nonengulfing particles. (Reprinted from A. P. Romio, C. Sayer, P. H. H. Araújo, M. Al-Haydari, L. Wu, and S. R. P. da Rocha, Macromolecular Chemistry and Physics 210:747–51, 2009. With permission.)

preformed poly­mer. One difference in this latter case is that phase separation is facilitated by the lower viscosity of the liquid compared to that of a preformed poly­mer. When hydrophobic liquids are to be encapsulated by a poly­mer shell, direct miniemulsion poly­mer­i­za­tion may be applied (Tiarks et al. 2001; Crespy et al. 2006, 2007; Luo and Gu 2007; Romio, Bernardy et al. 2009; Romio, Sayer et al. 2009). In this case, the hydrophobe and monomer form a homogenous organic phase, which is miniemulsified in the aqueous phase, and phase separation in the organic phase occurs throughout the poly­mer­i­za­tion. Figure 2.5 (a and b) shows micrographs of polystyrene (Tiarks et al. 2001) and poly(methyl methacrylate) (Romio, Sayer et al. 2009) nanocapsules synthesized via miniemulsion poly­mer­i­za­tion. A special case of core-shell particles are the onion-like morphologies. This kind of structure can be obtained when block copolymers (of two immiscible homopolymers) are formed. Kagawa et al. (2005) synthesized

46

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

2 µm

PEC

TEC NEC

1 µm (b) Figure 2.5 (continued).

(b)

(a)

200 nm

200 nm

Figure 2.6 TEM micrographs of ultrathin cross sections of PiBMA-b-PS particles, stained with RuO4 vapor for 30 min, prepared by seeded-ATRP with PiBMA-Br particles prepared by miniemulsion ATRP at Tween 80 concentrations of (a) 3 and (b) 6 wt% based on iBMA. (Reprinted from Y. Kagawa, H. Minami, M. Okubo, and J. Zhou, Polymer 46: 1045–49, 2005. With permission.)

s­ ubmicron-sized poly(i-butyl methacrylate)-block-polystyrene particles with an onion-like multilayered structure (Figure  2.6) using a two-step atom transfer radical poly­mer­i­za­tion (ATRP) in aqueous media: ATRP in miniemulsion to obtain the PiBMA seed particles followed by ATRP in seeded styrene emulsion poly­mer­i­za­tion.

Synthesis of Polymer Particles with Core-Shell Morphologies

47

2.3.3 Microemulsion Polymerization In the same way as emulsion poly­mer­i­za­tion, two-stage microemulsion poly­ mer­i­za­tion may also be used to synthesize CS particles. In this poly­mer­i­za­tion technique, extremely small monomer droplets (10–30 nm) forming a thermodynamically stable microemulsion are obtained by the combination of high surfactant (and cosurfactant) and relatively low monomer concentrations. The advantage of this two-stage microemulsion poly­mer­i­za­tion technique is related to the small sizes and, consequently, high superficial area of the particles that favors radical and monomer entry in detriment to undesired nucleation during the second stage of the poly­mer­i­za­tion. Nonetheless, CS particle synthesis by this technique shows the same drawbacks related to the low monomer content (0–10 wt%) and low monomer:surfactant ratio of other microemulsion poly­mer­i­za­tions. This technique has been used by Jang and Ha (2002) to prepare CS particles of 30 nm in size formed by PMMA core and PS shell with triblock copolymers of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) [(EO)x(PO)y(EO)x] as surfactant. These CS particles were subsequently treated with a selected solvent to remove the PMMA in order to obtain nanosized hollow polystyrene microlatexes. 2.3.4 Dispersion Polymerization Seeded dispersion poly­mer­i­za­tion is another technique that may be applied for the synthesis of particles with core-shell structures with average particle diameters in the range of 1 to 30 μm. In dispersion poly­mer­i­za­tion, the monomer is completely miscible with the continuous phase that is also composed by one or more nonreactive components, usually an alcohol as methanol or ethanol with or without water and that contains a stabilizer, as for instance poly(vinyl pyrrolidone) and the initiator. As a consequence, dispersion poly­mer­i­za­tion starts as a homogeneous poly­mer­i­za­tion, but, since the poly­mer formed throughout the poly­mer­i­za­ tion is not soluble in the continuous phase, it precipitates, forming colloidal particles that are stabilized by the added stabilizer. Thus, poly­mer­i­za­tion takes place in both continuous and particle phases, in degrees that may be varied, depending on the partitioning of monomer and radicals between these phases. Okubo and Izumi (1999) synthesized PMMA/PS CS particles by seeded dispersion poly­mer­i­za­tion and showed that, when the reaction temperature is below the glass transition temperature of the seed particles, this technique has the advantage of producing core-shell poly­mer particles in which layers accumulate in their order of production (kinetic control of morphology), regardless of the hydrophobicity of polymers forming core and shell, even if the morphology is thermodynamically unstable. This is attributed to the enhanced solubility of the second-stage monomers in the continuous phase

48

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

(due to the presence of an alcohol) combined with the high glass transition temperature of the seed poly­mer and fast adsorption of poly­mer radicals and inactive chains formed in the continuous phase onto the seed particles. When, however, the rate of adsorption of poly­mer radicals and inactive chains formed in the continuous phase onto the seed particles is slow, the second-stage poly­mer has the tendency to form clusters on the surface of the seed particle, and particles with different morphologies, egg-, snowman-, and confetti-like, may be formed (Fujibayashi et al. 2008). 2.3.5 Suspension Polymerization Suspension poly­mer­i­za­tion is a process in which the poly­mer­i­za­tion of relatively water-insoluble monomer droplets formed by vigorous stirring in the presence of a steric stabilizer leads to an aqueous dispersion of poly­mer particles in the size range of 50 to 1500 µm. To obtain CS particles by suspension poly­mer­i­za­tion, a two-step procedure should be employed, where the seed particles are obtained by suspension poly­mer­i­za­tion and the second-stage monomer is added afterward. The large particle size of the suspension poly­ mer­i­za­tion particles, and the consequently low superficial area, do not favor second-stage monomer absorption; as a consequence, undesired secondary particle nucleation is hard to avoid (Gonçalves et al. 2008a). In addition, if large amounts of second-stage monomer are used to swell seed particles, shear forces inside the reactor may lead to the undesired breakage of the swollen seed particles. And, even with small amounts, if this second-stage monomer concentrates at the outer layers of the seed particles due to slow monomer diffusion inside the particles, this would turn the particle surface very sticky and could lead to particle agglomeration. As a consequence, the synthesis of CS particles via suspension poly­mer­i­za­tion is a quite difficult and challenging task. Gonçalves et al. (2008b) synthesized large polystyrene (PS)/poly(methyl methacrylate) (PMMA) CS-structured particles by seeded (PS seeds) suspension poly­mer­i­za­tion of MMA in which the shell was composed by PMMA clusters densely dispersed in the PS matrix. The size and concentration of these clusters (shell) decreased from the outer shell to the core, and particle morphology was largely controlled by limitations to the diffusion of MMA through the poly­mer particle. As a consequence, thicker shells with a higher amount of incorporated PMMA were obtained by increasing the swelling time. Figure 2.7 shows a TEM micrograph and infrared (IR) data of the cross section of a particle. IR data confirm that the concentration of PMMA, denoted by the intensity of carbonyl absorption bands at 1740 cm–1, reached maximum values near the particle surface and decreased along the particle radius. An alternative for the synthesis of large particles with CS structures is the combination of suspension and emulsion poly­mer­i­za­tion to synthesize, respectively, the core and shell of the particles (Lenzi et al. 2003; Zhenqian

49

Synthesis of Polymer Particles with Core-Shell Morphologies

5 µm

5 µm

5 µm

(a) Figure 2.7 (a) TEM micrographs and the approximated representation of the cross section (stained with RuO4, PMMA appears as light gray and PS as dark gray; 6000x). (b) FTIR spectra of the cross section of a typical core-shell particle obtained with swelling time of 0 min and 0.23 mol% of BPO. (Reprinted from O. H. Gonçalves, J. M. Asua, P. H. H. Araújo, and R. A. F. Machado, Macromolecules 41: 6960–64, 2008. With permission.)

et al. 2009). In this case, the shell is composed by small aggregated emulsion poly­mer­i­za­tion particles, and the CS particles did not present a smooth spherical shape. 2.3.6 Other Techniques Several other techniques have also been described for the formation of CS particles. For instance, the preparation of preformed poly­mer blends in nanoor microparticles through the dissolution of both polymers in a common solvent followed by either the Shirasu porous glass membrane (SPG) emulsification technique (Ma et al. 1999, 2003), emulsification (Tanaka et al. 2008), miniemulsification using high-energy devices (Kietzke at al. 2007), or the nanoprecipitation technique always requires subsequent solvent evaporation

50

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

0.12 0.10

0.06 0.04 0.02

w

1820 1800 1780 1760 1740 1720 1700 1680 1660 1640

intensity

0.08

–1

cm r(

be

um

en av

P1

P2

P3

P4

P5

P6

P7

0.00 P8

)

(b) Figure 2.7 (continued).

after the dispersion of the organic phase in the aqueous phase. The two former methods lead to the formation of hybrid microparticles, whereas the two latter methods may be used to form hybrid nanoparticles. In all four cases, particles with CS structures may be attained only if this is the equilibrium morphology. The SPG emulsification technique with dichloromethane (DCM) as solvent for the preformed polymers, lauryl alcohol (LOH) as costabilizer, and poly(vinyl alcohol) and sodium lauryl sulfate in the aqueous phase has been reported for the preparation of uniform composite polystyrene/poly(methyl methacrylate) microspheres with diameters around 10 μm (Ma et al. 1999). The morphology of the composite particles was varied by the amount of LOH and by the PMMA:PS ratio, as shown in Figure 2.8. Polymer microcapsules have also been produced by applying microfluidic devices using capillary instability-driven break-up of a liquid jet formed by two immiscible fluids (oil and monomer) followed by photopoly­mer­i­za­tion of the monomeric shells (Nie et al. 2005), resulting in precise control of core number, location, and diameter, as well as shell thickness. Finally, particles having hollow structures, either core-shell or multihollow, have also been synthesized by water-in-oil-in-water (W/O/W) emulsion poly­mer­i­za­tion (Kim et al. 1999) and by a modified emulsion poly­mer­i­za­tion with a watermiscible alcohol and a hydrocarbon nonsolvent for the poly­mer (McDonald et al. 2000).

Synthesis of Polymer Particles with Core-Shell Morphologies

51

(b) 402

(a) 398

10 µm

10 µm

(c) 396

10 µm

(e) 402

1 µm

(d) 398

(f ) 396

1 µm

1 µm

Figure 2.8 Optical micrographs of droplets (a–c) and TEM micrographs of embedded cross section with RuO4 vapor staining of particles (d–f) as a function of the PMMA:PS ratio when 11.9 ml of DCM and 0.1 ml of LOH were used for 0.24 g of poly­mer (PMMA and PS). PMMA/PS (w/w): (a, d) 5/5, (b, e) 4, 6, and (c, f) 1/9. (Reprinted from G. H. Ma, M. Nagai, and S. Omi, Journal of Colloid Interface Science 219: 110–28, 1999. With permission.)

52

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

2.4 Characterization of Core-Shell Particles The characterization of core-shell particles includes determining the particle shape and the composition of the particle surface and the particle interior. Although microscopy data is required to make definite conclusions about particle morphology, according to Stubbs and Sundberg (2008), no single analytical technique is able to provide all the relevant details about the particle structure, but different techniques are required to adequately characterize the morphology of a given system, even for relatively simple systems. There are several relevant characterization techniques used for particle morphology determination including the direct microscopic techniques such as: TEM (transmission electron microscopy), AFM (atomic force microscopy), and SEM (scanning electron microscopy). Other indirect analyses could be performed by NMR (nuclear magnetic resonance), DSC (differential scanning calorimetry), and IR spectroscopy. And to characterize the latex particle surface, conductometric titration, among others, could also be used. The choice of the techniques used to characterize the core-shell latexes depends on whether the poly­mer particle is being characterized with respect to shape, structure, and/or surface. 2.4.1 Transmission Electron Microscopy TEM is the most widely used technique to characterize core-shell latexes (Gaillard et al. 2007) because a direct image of the structure can be obtained. However, the quality of the results obtained by TEM is a direct result of the sample preparation methods employed and the fact that this technique requires a high level of operator skill (Stubbs and Sundberg 2005b). TEM imaging presents several difficulties due to film formation during sample preparation of latex of low Tg, the weak contrast between the different phases and/or between the particles and the background, and their poor electron beam resistance, causing the deformation of the poly­mer particle during the analysis (Egerton et al. 2004). Most poly­mer analyses are carried out at accelerating voltages of 80 or 100 kV, although several polymers, like acrylic polymers, are more susceptible to radiation damage. Therefore, some limitations of TEM analysis are imposed by the poly­mer system. According to Gaillard et al. (2007), these difficulties could be overcome by using low temperature and/or low exposure to strong electron beam techniques and specimen preparation methods, like chemical staining, avoiding film formation, and stabilizing and enhancing the contrast between the different poly­ mer phases. Cold-stage holders could be used to investigate the particle morphology of low-Tg latex or microgels’ core-shell particles (Ballauff and Lu 2007) because

Synthesis of Polymer Particles with Core-Shell Morphologies

53

dispersions can be frozen, placed into TEM, and imaged. The low temperature also has the advantage of reducing radiation damage that occurs with all polymers (Dimonie et al. 1997). Chemical staining of the poly­mer particles generally has the advantage of hardening many types of poly­mer, which may facilitate specimen preparation and observation. To enhance the contrast between the particles and the background, “negative” staining with phosphotungstic acid (PTA) or uranyl acetate (UAc) is largely applied where the “negative” stain chemically interacts with the carbon film that covers the TEM grid. “Negative” staining is preferably used with latex particles not having reactive groups and that are not stable in the microscope or that are film forming (Karlsson and Schade 2005) like poly(vinyl acetate). “Positive” staining occurs when the chemical stain interacts directly with the poly­mer specimen by diffusion or reaction; the main use of selective “positive” staining with heavy elements (Ru, Os, tungsten, and uranium) is to increase high-angle Rutherford scattering, generating contrast between the stained and the unstained regions of the poly­ mer particle (Ferguson et al. 2002). The most common “positive” chemical staining agents are: osmium tetra oxide, OsO4, which is applied for unsaturated polymers that present residual allylic double bonds such as natural rubber-based latexes or polybutadiene; and ruthenium tetroxide, RuO4, which is more reactive than OsO4 and will react with double bonds in phenyl rings and with amine groups besides allylic double bonds (Trent 1984). RuO4 is particularly useful in morphological studies of multicomponent particles containing polystyrene in one of the phases (Stubbs et al. 1999). To avoid distortion of film-forming latex particles during drying, staining can be done in the liquid phase by adding the positive stain solution to a diluted latex dispersion (Karlsson et al. 1995). The combination of “positive” and “negative” staining methods is also useful to reveal internal structures and to fixate film-forming latexes like PS-PVAc core-shell latex where UAc is used for negative staining and RuO4 for staining the PS phase (Ferguson et al. 2002). Another way to increase the contrast between the poly­mer phases is to resolve one of the phases under exposure of a strong electron beam (200 kV) due to preferential degradation of one of the poly­mer phases. This is particularly true for PMMA/PS core-shell particles (Okubo and Izumi 1999) because PMMA homopolymers are significantly more beam sensitive than styrenic polymers; therefore, there will be a preferential beam-induced mass loss in the MMA-rich copolymer phase. Embedding and sectioning are sample preparation methods that enable one to cut the sample sufficiently thin for the microscope to increase its resolution (Karlsson and Schade 2005). In this technique, dried latex particles are embedded in epoxy resins and cured at room temperature. The cured epoxy/particle blend is then ultramicrotomed to obtain sections in the order of 50–100 nm.

54

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

2.4.2 Scanning Electron Microscopy Compared to TEM, the resolution of SEM is lower but detailed images of particle surface can be obtained resulting in information regarding size, shape, and structure. High-resolution field emission SEM (FESEM) presents a much higher resolution than conventional SEM using a thermionic emitter (Karlsson and Schade 2005). Typically, the poly­mer dispersion is dried down onto a stub; and to increase the resolution of nonconductive poly­mer, specimen is sputter coated with a ~10- to 20-nm-thick layer of gold or palladium. To observe the different phases in a poly­mer blend, one of the poly­mer phases could be selectively chemically etched off to achieve topographical differences that could be imaged by SEM. However, this is normally not employed on particles obtained by emulsion poly­mer­i­za­tion due to the submicrometric dimensions of these particles. 2.4.3 Atomic Force Microscopy AFM can be used to determine the surface structure of poly­mer particles because it presents a much higher resolution than SEM, making it a very useful tool to study film formation of poly­mer dispersions. No vacuum is needed and no difficult preparation is involved. However, the direct use of AFM for studying single particles has not been widely employed, partly because not all dispersions are suitable for morphology studies by AFM as the poly­mer particle should present at least one accessible low-Tg phase in order to reveal internal morphologies (Karlsson and Schade 2005). 2.4.4 Additional Techniques Used for Particle Characterization Other techniques can be used to complement the information obtained from the direct microscopic techniques. Many of these techniques may be applied in films made from structured latex particles. NMR methods (1H spin-diffusion measurements) can be used in latex films to characterize the interface of two immiscible poly­mer phases and its thickness (Landfester et al. 1996). Careful interpretation of thermal analysis data from DSC can indicate the relative extent of phase separation within the structured latex particles by comparing the size of the ΔCp transitions in DSC for films of latex particles to the transitions for the same pure bulk poly­mer (Stubbs and Sundberg 2005a). Because IR spectroscopy is sensitive to poly­mer composition, it can be used to investigate the structure of core-shell latexes and to deduce the thickness of the interfacial layer from spectral characteristics (Lange et al. 1988). Besides that, when poly­mer particles are large enough, as particles produced by suspension poly­mer­i­za­tion, IR spectroscopy could be employed to quantify poly­mer composition along the particle radius (Gonçalves et al. 2008b).

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55

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Landfester, K., Boeffel, C., Lambla, M., and H. W. Spiess. 1996. Characterization of interfaces in core-shell polymers by advanced solid-state NMR methods. Macromolecules 29:5972–80. Lange, J., Hergeth, W.-D., and S. Wartewig. 1988. Infrared spectroscopy of polymeric core-shell latexes. Acta Polymerica 39:479–81. Lee, D. I., and T. Ishikawa. 1983. The formation of “inverted” core-shell latexes. Journal of Polymer Science, Polymer Chemistry Edition 21:147–54. Lenzi, M. K., Silva, F. M., Lima, E. L., and J. C. Pinto. 2003. Semibatch styrene suspension poly­mer­i­za­tion. Journal of Applied Polymer Science 89:3021–38. Li, M., Daniels, E. S., Dimonie, V., Sudol, E. D., and M. S. El-Aasser. 2005. Preparation of polyurethane/acrylic hybrid nanoparticles via a miniemulsion poly­mer­iz­ a­ tion process. Macromolecules 38:4183–92. López, A., Chemtob, A., Milton, J. L., Manea, M., Paulis, M., Barandiaran, M. J., Theisinger, S., Landfester, K., Hergeth, W. D., Udagama, R, Mckenna, T., Simal, F., and J. M. Asua. 2008. Miniemulsification of monomer-resin hybrid systems. Industrial Engineering and Chemistry Research 47:6289–97. Lovell, P. A., and M. S. El-Aasser. 1997. Emulsion poly­mer­iz­ a­tion and emulsion polymers. New York: John Wiley & Sons. Luo, Y., and H. Gu. 2007. Nanoencapsulation via interfacially confined reversible addition fragmentation transfer (RAFT) miniemulsion poly­mer­i­za­tion. Polymer 48:3262–72. Ma, G. H., Nagai, M., and S. Omi. 1999. Effect of lauryl alcohol on morphology of uniform polystyrene-poly(methyl methacrylate) composite microspheres prepared by porous glass membrane emulsification technique. Journal of Colloid and Interface Science 219:110–28. Ma, G. H., Su, Z.G., Omi, S., Sundberg, D., and J. Stubbs. 2003. Microencapsulation of oil with poly(styrene-N,N-dimethylaminoethyl methacrylate) by SPG emulsification technique: Effects of conversion and composition of oil phase. Journal of Colloid and Interface Science 266:282–94. McDonald, C. J., Bouck, K. J., and A. B. Chaput. 2000. Emulsion poly­mer­i­za­tion of voided particles by encapsulation of a nonsolvent. Macromolecules 33:1593–1605. Nelliappan, V., El-Aasser, M. S., Klein, A., Daniles, E. S., and J. E. Roberts. 1996. Compatibilization of PBA/PMMA core/shell latex interphase. II. Effect of PMMA macromonomer. Journal of Polymer Science, Part A: Polymer Chemistry 34:3183–90. Nie, Z., Xu, S., Seo, M., Lewis, P. C., and E. Kumacheva. 2005. Polymer particles with various shapes and morphologies produced in continuous microfluidic reactors. Journal of American Chemical Society 127:8058–63. Nomura, M., Tobita, H., and K. Suzuki. 2005. Emulsion poly­mer­i­za­tion: kinetic and mechanistic aspects. In Advances in poly­mer science, vol. 175, Polymer particles, ed. M. Okubo, 1–128. Berlin-Heidelberg: Springer-Verlag. Okubo, M., and J. Izumi. 1999. Synthesis of micron-sized monodispersed, core-shell composite poly­mer particles by seeded dispersion poly­mer­i­za­tion. Colloids and Surfaces A: Physiochemical Engineering Aspects 153:297–304. Piirma, I. 1982. Emulsion poly­mer­i­za­tion. New York: Academic Press. Rajatapiti, P., Dimonie, V. L., and M. S. El-Aasser. 1997. Latex particle morphology: The role of macromonomers as compatibilizing agents. In Polymeric dispersions: Principles and applications, ed. J. M. Asua, 189–202. Drodrecht: Kluwer Academic Publishers.

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3 Advanced Polymer Nanoparticles with Nonspherical Morphologies Yongxing Hu, Jianping Ge, James Goebl, and Yadong Yin Contents 3.1 Introduction................................................................................................... 62 3.2 Overview of Approaches to Nonspherical Polymer Nanoparticles Synthesis........................................................................................................63 3.3 Synthesis of Nonspherical Polymer Particles via Polymerization.........64 3.3.1 Phase Separation and Seeded Emulsion Polymerization...........64 3.3.1.1 Mechanism..........................................................................64 3.3.1.2 Thermodynamics of Swelling and Phase Separation............................................................................ 66 3.3.1.3 Kinetics of Phase Separation............................................ 68 3.3.1.4 Shape Control..................................................................... 69 3.3.1.5 Complex Structures through Multistep Polymerization................................................................... 70 3.3.1.6 Particles with Anisotropic Properties............................. 73 3.3.2 Solvent Evaporation and Seeded Dispersion Polymerization.................................................................................. 76 3.4 Physical Posttreatment Approaches........................................................... 78 3.4.1 Stretching........................................................................................... 79 3.4.1.1 Simple 1D Stretching......................................................... 79 3.4.1.2 Modified Stretching Scheme............................................ 81 3.4.1.3 2D Stretching......................................................................83 3.4.2 Compression...................................................................................... 86 3.4.3 Self-Assembly.................................................................................... 87 3.4.3.1 Self-Assembly in Soft Templates...................................... 87 3.4.3.2 Self-Assembly in Hard Template..................................... 91 3.5 Summary........................................................................................................ 92 References................................................................................................................ 93

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3.1 Introduction Polymer particles have been the subject of research in various fields for several centuries. The discovery of rubber latex, a class of naturally occurring colloidal dispersions of cis-polyisoprene particles, is usually regarded as the starting point of the development of modern poly­mer science (Whitby et al. 1933; Hohenstein et al. 1946). Driven by the need for rubber polymers, in the early twentieth century extensive research was carried out in order to find synthetic routes to polymers by mimicking Mother Nature’s process for producing natural rubber (Hofmann 1912; Gottlob 1910, 1912; Pond 1914). In 1912, Kurt Gottlob invented the first process that enabled the preparation of synthetic rubber latex by poly­mer­i­za­tion of isoprene in viscous aqueous solutions. The process involves the use of naturally occurring polymers such as gelatin, egg albumin, and starch to stabilize a dispersion of monomer droplets, which are then poly­mer­ized into solid particles. This process, now widely known as “emulsion poly­mer­i­za­tion,” has since become one of the dominant methods for synthesizing poly­mer particles from a wide variety of monomer materials. In most cases, the particles produced using emulsion poly­mer­i­za­tion or related processes have sizes within the range of 100 nm to 1 µm, although it is not uncommon to find recipes for making particles beyond this range. In this chapter, the term “nanoparticle” is used to broadly cover particles with sizes of a few nanometers to several micrometers. Polymer nanoparticles play an important role in worldwide commerce as well as scientific studies. Because of their versatile properties and applications, they are omnipresent parts of our daily life, with uses in paper making, paints and coatings, adhesives, textile processing, and also medical and pharmaceutical products (Xia et al. 2000). In fundamental research, poly­mer nanoparticles have been used as an interesting model system for studying the behavior of atoms because many of the forces that govern the structure and behavior of matter, such as excluded volume interactions or electrostatic forces, govern the structure and behavior of poly­mer particle suspensions. For example, the phase transitions in liquid are analogous to those in poly­ mer nanoparticle suspensions, which can be studied conveniently in real time using optical techniques. Due to the ease of making uniform samples with well-controlled sizes, recently poly­mer nanoparticles have become popular candidates for sacrificial templates in fabrication of functional nanostructures such as core-shell and hollow spheres. Many procedures have been developed to coat poly­mer particles with various materials such as metal, semiconductor, or inorganic-organic hybrid layers to imbue them with new properties while at the same time retaining the sample uniformity. The high monodispersity that is achievable with poly­mer nanoparticles has also gained them an important role in the exciting field of colloidal crystals. Similar to silica colloids, uniform poly­mer particles can self-assemble

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into highly ordered three-dimensional arrays over a very long range (Sutera et al. 1980) to form artificial crystals that appear analogous to their atomic or molecular counterparts. When the periodicity of the array is of the same order of magnitude as the wavelength of visible light, such colloidal crystals display brilliant iridescence, which can be attributed to the constructive interference of light waves as the result of interaction with the particle arrays. Macroporous materials have been produced by combining colloidal crystals with suitable structure-forming precursors, followed by selective removal of the poly­mer nanoparticle template from the solid composite by chemical or thermal methods. The resulting products are inverse replicas of the particle arrays, which can be viewed as three-dimensional structures of interconnected macropores with regular spacing and long-range order. Driven by the minimization of interfacial energy, the majority of poly­mer nanoparticles have been limited to spherical shapes. Spherical colloids have been the dominant subject of research in colloidal science for many decades because of the ease of production as monodispersed samples. However, it has been recently realized that spherical particles are not necessarily the best option for fundamental studies or practical applications that are associated with these materials. For example, they have limited use for modeling the interparticle interactions and hydrodynamic behaviors of various irregular colloidal particles that are commonly found in industrial products. When they are used as building blocks in fabricating three-dimensional colloidal crystals, they can provide only a very limited set of crystal structures. Crystals assembled from spherical colloids can have only incomplete photonic bandgaps, which do not allow full control of the propagation of light in all three dimensions (Lu et al. 2001). In these regards, nonspherical colloidal particles are believed to offer some immediate advantages over their spherical counterparts in applications that require lower symmetries and higher complexities. For example, core-shell particles produced using nonspherical poly­mer cores will inherit the anisotropic shape, which in many cases adds an additional parameter for tuning the physical properties of the material. In the case of colloidal photonic crystals, it has also been remarked theoretically that a face-centered cubic colloidal crystal composed of nonspherical particles could possess a complete bandgap if the relative orientation of the nonspherical particles met certain requirements (Lu et al. 2001, 2002).

3.2 Overview of Approaches to Nonspherical Polymer Nanoparticles Synthesis Since a sphere is the energetically most favorable shape for liquid droplets, nonspherical particles are rarely seen as products in the standard

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emulsion poly­mer­i ­za­t ion processes. Interestingly, however, emulsion poly­mer­i ­za­t ion still serves as the starting point for the synthesis of most nonspherical poly­mer particles. Generally, there are two important approaches for synthesizing nonspherical poly­mer nanoparticles: one refers to the direct synthesis, which involves swelling and phase separation processes in an emulsion poly­mer­i ­za­t ion system; the other refers to the indirect approach, which utilizes the physical posttreatment of preformed spherical poly­mer particles. Strictly speaking, the first approach is also indirect because the initial products in the emulsion poly­mer­i­za­tion are spherical particles, which transform to nonspherical shapes following the additional swelling and poly­mer­i­za­ tion steps. We classify it as a “direct synthesis” because in most cases these steps can be completed in one pot without the need for significant changes in the chemical environment. The transformation is due to differential interfacial tension between the preexisting cross-linked poly­mer particles and the absorbed monomer swelled in the polymeric matrix. By controlling the degree of cross-linking and the swelling processes, nonspherical particles with different asymmetries can be prepared. In the second approach, the spherical poly­mer precursors are first synthesized using standard emulsion processes and then transformed into different nonspherical shapes through posttreatment, which involves either physical deformation or controlled assembly processes. The posttreatment of preexisting structures includes a group of efficient methods that are able to yield particles with complex shapes/structures that are usually inaccessible by direct synthesis methods. In one of the typical indirect methods, pre­ prepared particles first can be heated above their glass transition temperature (Tg) and then deformed to form anisotropic particles with distinct shapes using physical techniques such as mechanical stretching. By controlling the direction and degree of deformation, a variety of shapes can be obtained. Another typical indirect method utilizes self-assembly approaches to organize poly­mer nanoparticles to form anisotropic structures and then applies a post physical or chemical method to fix the structures.

3.3 Synthesis of Nonspherical Polymer Particles via Polymerization 3.3.1 Phase Separation and Seeded Emulsion Polymerization 3.3.1.1 Mechanism Emulsion poly­mer­i­za­tion is a powerful method for the production of uniform spherical poly­mer particles. It is typically a radical poly­mer­i­za­tion

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65

process that occurs in an emulsion incorporating water, monomer, and surfactants. The most common type of emulsion poly­mer­i­za­tion is an oil-inwater emulsion, in which droplets of monomer (the oil) are emulsified with surfactants in a continuous phase of water. Since its discovery, this process has been widely employed for the preparation of monodispersed spherical nanoparticles from a wide range of poly­mer materials. However, its application in the synthesis of nonspherical particles is very difficult because the spherical shape is more favorable in terms of free energy. This limitation has been overcome by a seeded emulsion poly­mer­i­za­tion method, which was discovered by Ugelstad et al. (Skjeltorp et al. 1986) and further developed by Sheu, El-Aasser, and Vanderhoff (1990a, 1990b) and then Weitz, and Gilbert et al. (Kim et al. 2006, 2007; Mock et al. 2006). After ~30 years of development, it is now an effective method for synthesizing various poly­mer particles with anisotropic characteristics in both shape and physical properties. Essentially, this method utilizes the phase separation of swelling monomers from the cross-linked poly­mer seeds followed by poly­mer­i­za­tion at elevated temperature to produce nonspherical particles. A general mechanism for the phase separation and domain formation is discussed in this section, followed by a detailed discussion of its thermodynamics and kinetics, to present a clear first image of the major procedures (Sheu et al. 1990a, 1990b). As shown in Figure  3.1, the synthesis generally starts with cross-linked poly­mer particle seeds, also called latex interpenetrating poly­mer networks (IPNs), which can be prepared by conversional emulsion poly­mer­i­za­tion methods (Stage 1). Upon mixing with monomers, the poly­mer seeds are gradually swollen until an equilibrium state is reached at room temperature, at which the monomer-poly­mer mixing force is balanced with the elastic force of the poly­mer network and the particle-liquid interfacial tension 1

2 ∆

+

6

3

5

4

Figure 3.1 Schematic illustration of the monomer swelling and phase separation in a seeded emulsion poly­mer­i­za­t ion process. (Reprinted from H. R. Sheu, M. S. Elaasser, and J. W. Vanderhoff, Journal of Polymer Science, Part A: Polymer Chemistry 28: 629, 1990. With permission.)

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(Stage 2). With increasing temperature, the balance is broken due to the increased ­elastic-retractive force of the poly­mer chains, the decreased viscosity of the poly­mer phase, and thereby the enhanced mobility of monomers and short-chain linear polymers. As a result, the monomers and linear polymers are expulsed from the IPN upon heating and form a new phase domain adhered to the seeds (Stage 3). The new phase domain grows by absorption of monomer from the seed domain and is simultaneously poly­ mer­ized until the forces are balanced again for both domains (Stages 3–5). Finally, nonspherical poly­mer particles with two well-defined domains are formed at the end of the poly­mer­i­za­tion (Stage 6). 3.3.1.2 Thermodynamics of Swelling and Phase Separation It has been demonstrated that raised temperature will enhance the phase separation of monomers and linear polymers from an interpenetrating poly­ mer network, thus forming a liquid bulge adhered to the seed particle and further polymerizing into nonspherical particles. Sheu and El-Aasser et al. have developed a thermodynamic model to explain the swelling and phase separation through a comprehensive consideration of the monomer-poly­mer mixing force, the elastic retraction from the stretching of chains in crosslinked poly­mer networks, and the surface tension at the particle-solution interface (Sheu et al. 1990a). This model is built based on a physical fact that the chemical potential ΔGm,p of monomer in the particle phase is equal to that ΔGm,a in the aqueous phase when the swelling is at the equilibrium state. For monomers like styrene, whose solubility in water is extremely low, ΔGm,a is often negligible such that ΔGm,p approximately equals zero at the balanced state. The chemical potential of monomer in the particle phase can be considered as the sum of three ­contributions, including the monomer-poly­mer mixing force ΔGm, the elastic force of cross-linked poly­mer network ΔGel, and the surface tension at the particle-water interface ΔGt.

∆G m , p = ∆G m + ∆G el + ∆Gt = 0

(3.1)

Here, ΔGm = RT[ln(1 – νp) + νp + χmpνp2] according to the Flory-Huggins expression, ΔGel = RTNVm(νp1/3 – νp/2) according to the the Flory-Rehner equation, and ΔGt = 2Vmγ/r according to the Morton equation, R is the gas constant, T is the absolute temperature, νp is the volume fraction of poly­mer in the swollen particle, χmp is the monomer-poly­mer interaction parameter, N is the effective number of chains per unit volume, Vm is the molar volume of the monomer, γ is the particle-water interfacial tension, and r is the radius of the swollen particles. In a typical instance, where a cross-linked polystyrene (PS) seed 5.2 μm in diameter is swelled with styrene, the values of ΔGm/RT, ΔGel/RT, and

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67

0.01

∆Gm/RT, ∆Gel/RT, and ∆Gt/RT

0 ∆Gt RT

–0.01 ∆Gm RT

–0.03

∆Gel RT

–0.05 –0.07 –0.09 –0.11

0

0.10

0.20

VP

0.30

0.40

0.50

Figure 3.2 Relationship between the poly­mer volume fraction and the changes of each partial molar free energy (ΔGm/RT, ΔGel/RT, ΔGt/RT). (Adapted from H. R. Sheu, M. S. El-Aasser, and J. W. Vanderhoff, Journal of Polymer Science, Part A: Polymer Chemistry 28: 629, 1990. With permission.)

ΔGt/RT can be plotted as a function of poly­mer volume fraction νp, respectively (Figure 3.2). The mixing force ΔGm makes a negative contribution to the overall chemical potential, promoting the particle expansion and thereby further swelling of monomers. On the contrary, both the elastic force ΔGel and interfacial force ΔGt make positive contributions, which restrain the stretching of poly­mer chains and expansion of particles. For particles larger than 2 μm, the interfacial force is usually negligible compared to the elastic force, so that the swelling and phase separation are actually determined by the other two parameters. This thermodynamic model qualitatively explains the driving force of monomer swelling and phase separation. When the poly­mer seeds are mixed with a saturated solution of monomers, the latter is continuously absorbed into the former because the high initial poly­mer volume fraction νp in the poly­mer seeds results in negative chemical potential ΔGm,p that encourages the poly­mer seeds’ expansion. With further progress of swelling, the poly­ mer volume fraction νp decreases, and eventually the swelling stops when the chemical potential ΔGm,p reaches zero at room temperature. As the temperature is raised, the chemical potential ΔGm,p immediately increases and exceeds zero due to the increased retractive elastic force ΔGel, which contracts the swollen network and expels the monomer to form a new phase domain attached to the seed. The reduction of viscosity and enhancement of

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mobility upon heating in the poly­mer network also contribute to this phase separation process. The small new domain contains monomers at a higher concentration than that of the seed domain, and thereby possesses a higher poly­mer­i­za­tion rate and higher poly­mer volume fraction νp. The resulting low free energy of mixing and negative chemical potential ΔGm,p for the new domain facilitates the migration of monomer and further poly­mer­i­za­tion. Finally, the transportation of monomer ceases because of the decreased difference in monomer concentration in both domains, eventually resulting in poly­mer doublets. 3.3.1.3 Kinetics of Phase Separation Sheu and El-Aasser et al. have proven that the kinetics of phase separation are different for PS seeds with different degrees of cross-linking (Sheu et al. 1990a), as they noticed that lightly cross-linked seeds generally produced doublets, whereas highly cross-linked ones produced triplets and multi­ plets. In the case of lightly cross-linked PS seed (0.2% divinylbenzene [DVB]), the particle swollen with monomer retains its spherical shape throughout the swelling process, and its size stops increasing after 24 h (Figure  3.3). After the temperature is raised to 70°C for 2 min, a new domain appears due to the heat-induced retraction of poly­mer chains and expulsion of monomers. The new domain keeps growing while the seed shrinks, and they reach the same size after 177 min, forming a symmetric doublet. After 738 min, the new domain grows larger than the seed domain, which shrinks to a size slightly larger than its original dimensions. Finally, the poly­mer­i­ za­tion is completed after 1440 min with 100% conversion, producing asymmetric doublets (Figure 3.3h). By substituting monomer with toluene, Sheu and El-Aasser et al. confirmed that the phase separation is initiated by the a

b

c

d

e

f

g

h

20 µm

Figure 3.3 Optical microscopy images of 5.2-μm PS particles cross-linked with 0.20% DVB and swollen with styrene at 23.2°C for 1440 min (a), and the nonspherical particles after poly­mer­i­za­t ion at 70°C for (b) 2 min, (c) 77 min, (d) 97 min, (e) 177 min, (f) 390 min, (g) 738 min, and (h) 1440 min. (Reprinted from H. R. Sheu, M. S. El-Aasser, and J. W. Vanderhoff, Journal of Polymer Science, Part A: Polymer Chemistry 28: 629, 1990. With permission.)

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69

increase in temperature at the beginning of the poly­mer­i­za­tion, which is a quick process, and is further enhanced by the conversion from monomer to poly­mer in the new domain as the reaction proceeds. These two processes can be summarized as elastic-driven and poly­mer­i­za­tion-driven phase separation, respectively (Kim et al. 2006). Therefore, the entire phase separation can be considered as a burst in new domain generation, followed by further domain growth due to the monomer transportation and poly­mer­i­za­tion. In the case of highly cross-linked PS seeds, there are two remarkable characteristics that differ from the kinetic process with lightly cross-linked seeds. One is the early phase separation during the swelling process, which is believed to be caused by a progressive contraction of the poly­mer network as the chains are highly cross-linked. The second feature is the formation of multiple domains and multiplets. Once the temperature is raised, the new phase domain continues growing and some particles form additional domains. After poly­mer­i­za­tion, a mixture including some doublets, triplets, multiplets, and small free particles is produced. The formation of multiple domains is promoted when the degree of cross-linking in seeds is increased. This difference is attributed to the larger gel fraction and the formation of inhomogeneities in the highly cross-linked seed particles, which also localize the contraction because the diffusion of monomer is not fast enough to uniformize the monomer distribution in the poly­mer network before the creation of new domains. 3.3.1.4 Shape Control Various parameters including the degree of seed cross-linking, the monomer:poly­mer swelling ratio, temperature, seed size, and cross-linker level in swelling monomer contribute to the control over the shape of the nonspherical poly­mer particles (Sheu et al. 1990b). As summarized by Sheu and El-Aasser et al., the final products may vary from uniform spheres to ellipsoids, asymmetric and symmetric doublets, and multiplets through the manipulation of these parameters. Degree of seed cross-linking. As mentioned previously, the degree of seed cross-linking determines the elastic retraction and poly­mer chain conformation, which is critical for the proceeding of phase separation and homogeneity of swelling. Seeds with minimal cross-linking (0.06%) grow into larger spherical particles with no phase separation because the slightly increased elastic retraction upon heating is not strong enough to expel the monomer to form new phase domains. As the cross-linking increases (0.2–1.5%), the elastic retraction enhances upon heating and leads to phase separation, which eventually produces symmetric or asymmetric doublets. Besides these thermodynamic considerations, in a kinetic sense, a higher cross-link density indicates a larger fraction of the gel portion and a shorter poly­mer chain relaxation time, which also promote phase separation. As discussed earlier, when the seeds are highly cross-linked (2.0–6.0%), inhomogeneous swelling and localized contraction lead to the production of multiplets.

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Monomer:poly­mer swelling ratio. The degree of phase separation and the size of new phase domains increase with higher monomer:poly­mer swelling ratios, since the new domains grow by the absorption and poly­mer­i­za­tion of monomers transported from the seed domain until the chemical potentials of monomer in both domains become balanced. With a monomer:poly­ mer ratio of 1:1, no phase separation is observed and spherical particles are produced. A monomer:poly­mer ratio of 2:1 gives asymmetric doublets with a smaller new domain. Increasing the monomer:poly­mer ratio to 3:1 and 4:1 will produce symmetric doublets and asymmetric doublets with a larger new domain, respectively. Temperature. The reaction temperature is also a critical parameter for phase separation and poly­mer­i­za­tion. From a thermodynamic point of view, a higher poly­mer­i­za­tion temperature will cause a great increase in the retractive elastic force upon heating and a larger separated phase domain. In the kinetic sense, a higher temperature will increase the poly­mer chain relaxation time and lower the viscosity to accelerate the formation and growth of a new phase domain. It has indeed been observed that particles poly­mer­ized at 50°C grow to asymmetric doublets with smaller new domains, while those formed at 70°C contain an enlarged second domain. Size of seed particles. The size of the seed particles is important to the thermodynamics of phase separation because it directly affects the surface tension at the interface of the seed and the aqueous solution. According to the Morton equation ΔGt = 2Vmγ/r, a larger seed particle size leads to a smaller inter­ facial tension, which certainly enhances the phase separation. The 0.6-μm seed particles grow to spherical particles without phase separation, while 1.9-μm, 5.2-μm, and 8.1-μm seed particles change to uniform ellipsoids, symmetric doublets, and asymmetric doublets, respectively. Note that even for sub­micron scale seeds, it is still possible to create nonspherical particles when the degree of cross-linking of seed particles and the monomer:poly­ mer swelling ratio are sufficiently high. Cross-linker level of swelling monomer. Polymerization with no cross-linker (0% DVB) generates a latex semi-IPN, and with cross-linker produces a latex full-IPN as both the seed domain and new domain are cross-linked. The new domain shrinks as the cross-linker level increases in the monomer mixture, thus producing doublets with a smaller new domain. This occurs because the new domain with higher cross-linking has higher viscosity and stronger elastic retraction upon expansion, both of which limit the transportation of monomers from the seed domain. 3.3.1.5 Complex Structures through Multistep Polymerization In the previous section, the synthesis of basic nonspherical particles through swelling, phase separation, and poly­mer­i­za­t ion was discussed. However, it is of great interest to chemists and materials scientists to explore the possibility of fabricating more complex nonspherical poly­mer structures

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through this “seeded emulsion poly­mer­i­za­t ion” scheme. Recently, Weitz et al. advanced this technique by synthesizing a variety of uniform complex particles on a large scale through the tight control of the cross-linking density of the poly­mer network (Kim et al. 2007). Their synthesis starts with symmetric poly­mer doublets with controllable degrees of cross-linking in each domain, and utilizes the gradients in cross-linking density as the driving force to manipulate the direction of phase transfer, thus leading to the production of rod-, cone-, triangle-, and diamond-shaped particles after poly­mer­i­za­tion. The entire synthesis comprises three continuous seeded emulsion poly­mer­i­za­t ions, and the cross-linking degree of the seed and second domain of the doublets are adjusted by changing the concentration of cross-linker in the poly­mer­i­za­t ion of spherical seeds ([DVB]a) and doublets ([DVB]b), respectively. Since the IPN can be perfectly swelled in toluene, one can observe the swelling of dimers in toluene using optical microscopy and obtain the crosslinking density (ν) from the ratio of unswelled volume to the swelled volume (φ). According to the theory of Flory and Rehner, the cross-linking density can be calculated by the following equation, where NA is Avogadro’s number, V is the molar volume of the solvent, and χ is the poly­mer-solvent inter­action parameter. The dependence of cross-linking gradient (Δν) on the cross-linker ratio ([DVB]b:[DVB]a) can be plotted to investigate the influence of cross-­linking on the shape. It should be noted that in dimer particles, the cross-linking degree in the new domain (bulb b) can be estimated based on the concentration of cross-linker ([DVB]b) in the second reaction, where a small deduction must be considered as the poly­mer­i­za­tion also occurs in the original domain (bulb a). Accordingly, the cross-linking degree in the original domain (bulb a) is slightly larger than the one quantified with [DVB]a.

ν=

NA  ln(1 − φ) + φ + χφ 2  φ 1/3 − φ/2 V 

(3.2)

As shown in Figure 3.4, the gradient of cross-linking density (Δν) in dimers is critical to the shape of multiplets. IPN with high cross-linking density has been proven to generate stronger elastic retraction upon heating, thus facilitating the phase separation and new domain formation. When the degree of cross-linking of the second domain is as large as that of the original (ν b ≈ νa, Δν = 0.9 mol m–3), the elastic retractions in both domains are close enough that the new separated domain grows perpendicularly between the two bulbs, forming triangle-shaped particles. Decreasing the cross-linking density of the second domain in dimer seeds (ν b < νa, Δν = 15 mol m–3) will break the balance of elastic retraction upon heating, as the driving force of pushing the monomer mixture out of the original domain is stronger than that in the second domain. In other words, the gradient in cross-linking density drives the monomer mixture to flow down the gradient, leading to linear growth

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

(a)

(b)

(c)

(d)

45 ∆ν = νa – νb (mol  m–3)

40 35

5 µm

30 25 20 15 10 5 0 0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

[DVB]b/[DVB]a (e) Figure 3.4 (a–d) SEM images of (a) triple-rod particles prepared at [DVB]b/[DVB]a = 0.7; (b) triangular particles at [DVB]b/[DVB]a = 1.1; (c) cone particles made similar to the triple-rod particles except with a higher volume of monomer mixtures in the final swelling stage; (d) diamond-shaped particles made similar to the triangular particles but with 20% more total cross-linker; and (e) cross-linking density gradient (Δν) tuned by changing the concentration of DVB in each swelling step ([DVB]b and [DVB]a). Insets show the optical microscope images of dimer particles before (upper) and after (lower) swelling at different [DVB]b:[DVB]a ratio, and the schematic images of the final particles grown from these dimers. (Adapted from J. W. Kim, R. J. Larsen, and D. A. Weitz, Advanced Materials 19: 2005, 2007. With permission.)

Advanced Polymer Nanoparticles with Nonspherical Morphologies

73

and rod-shaped particles. Further decreasing the cross-linking density of the second domain in dimer seeds (ν b < νa, Δν = 37 mol m–3) will seriously weaken the elastic retraction, such that no phase separation occurs and asymmetric dimers are produced. When Δν is tuned between these critical values, mixtures of two types of particles are generated after poly­mer­i­za­tion. This procedure represents a general method for the preparation of uniform and high-yield poly­mer triplets in a one-batch reaction, and also holds the potential for chemical fabrication of more complex nonspherical poly­mer particles. Modifications to the recipes for rod- and triangle-shaped particles will produce additional complex particles. For instance, the cone-shaped particles can be produced similarly to the rod particles, but with a higher volume of monomer mixtures in the final swelling stage; while the diamondshaped particles can be synthesized similarly to the triangular particles, but with higher cross-link densities in both domains of dimer seeds ([DVB]a = 1.2 vol%, [DVB]b = 1.32 vol%). 3.3.1.6 Particles with Anisotropic Properties The preceding sections have discussed seeded emulsion poly­mer­i­za­tion as an effective strategy to produce various nonspherical poly­mer particles. Here, we will introduce poly­mer colloids with not only nonspherical shapes but also anisotropic physical properties. By surface modification and other chemical treatments, or incorporation of inorganic functional materials, this method can be extended to the preparation of polymeric particles with anisotropic properties, such as amphiphilic particles and magnetically anisotropic particles. Particles with chemical rather than shape anisotropy play an important role in recognizing specific molecules, self-assembling, and emulsion stabilization. One particular kind of useful anisotropy of chemical ­property is “amphiphilicity,” which is generally induced by organic groups or polymeric blocks. Recently, Weitz et al. have reported a flexible approach, based on phase separation and seeded emulsion poly­mer­i­za­tion, for the synthesis of uniform and amphiphilic nonspherical particles (Kim et al. 2006). The experimental procedure includes the synthesis of cross-linked poly(styrene-co-glycidyl methacrylate) (PS-co-PGMA) spherical particles, PS-co-PGMA/PS symmetric poly­mer doublets, and surface treatment with poly(ethylene imine) (PEI). Glycidyl methacrylate is copoly­mer­ized to the original PS seed to provide epoxy rings on the surface, which offer reactive sites for hydrophilic chemicals that have active hydrogen. Through swelling by styrene monomer solution, phase separation upon heating, and thermal poly­mer­i­za­tion, the spherical seeds turn into PS-co-PGMA/PS doublets. It is important that the PGMA chains stay in the original domain during phase separation so that the distribution of surface epoxy rings is extremely asymmetric in the doublets. The half-sphere functionalized with the epoxy rings is then reacted with hydrophilic PEI, turning the hydrophobic doublets into

74

a

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

b

c

Hydrophilic PEI PS PEI Hydrophobic PS 10 µm

10 µm

Figure 3.5 (a) SEM image of amphiphilic PS doublets obtained by the reaction of surface epoxy rings with PEI. (b) Fluorescence microscope image of fluorescein-labeled amphiphilic PS doublets. (c) Bright-field microscope image of the assembly of amphiphilic PS doublets at water/octanol interface. (Reprinted from J. W. Kim, R. J. Larsen, and D. A. Weitz, Journal of the American Chemical Society 128: 14374, 2006. With permission.)

amphiphilic structures. The PEI-coated part can then be labeled with fluorescein sodium salt and imaged using fluorescence microscopy to confirm the exact amphiphilic structure (Figure 3.5). Compared with the spherical amphiphilic Janus particle, these particles with both a nonspherical shape and amphiphilic properties may be more suitable to stabilize the interfaces and emulsion droplets. As shown in Figure 3.5, the water droplets inside 1-octanol can be stabilized by these colloid surfactants. The interface curvature and droplet size are expected to be conveniently tuned by controlling the geometry of the doublets. Besides selective surface modification to the premade nonspherical particles, incorporation of functional content into the poly­mer particle through core-shell fabrication is an alternative way to realize anisotropic properties. A series of spherical and nonspherical magnetite-PS composite colloids with anisotropic magnetic properties has been reported (Ge et al. 2007). In a typical process, 3-(methacryloyloxy)propyl trimethoxysilane (MPS)-modified Fe3O4@SiO2 particles are used as seeds to prepare concentric and eccentric Fe3O4@SiO2@PS core-shell particles through seeded emulsion poly­mer­i­za­ tion. The location of the Fe3O4@SiO2 core is determined by the degree of crosslinking in the poly­mer layer: the eccentric particles are prepared without the addition of DVB while concentric particles are obtained when the polymers are cross-linked. The formation of eccentric structure is due to the interfacial tension between the hydrophilic seed particle and the hydrophobic monomer (Park 2001; Minami et al. 2003; Mock et al. 2006). At the initial stage of poly­mer­i­za­tion, a thin layer of polystyrene shell is deposited in the form of small particles on the silica surface through copoly­mer­i­za­tion with the surface double bonds offered by MPS molecules. After absorbing hydrophobic monomers, the polystyrene chains in the shell tend to contract and reduce the surface area as a result of interfacial tension, leading to asymmetric distribution of poly­mer around the seeds (Figure 3.6a). Modification with MPS renders the silica surfaces considerable compatibility with the swollen poly­ mer shell so that the final products still maintain an overall spherical shape

Advanced Polymer Nanoparticles with Nonspherical Morphologies

a

b

c

d

e

f

g

75

h

400 nm

Figure 3.6 TEM images of (a) eccentric and (b) concentric spherical particles produced in one-step emulsion poly­mer­i­za­t ion, and evolution of doublets (c–f) prepared by swelling with particle b, phase separation, and poly­mer­i­za­t ion. Self-assembly of (g) concentric and (h) eccentric particles into chain structures in a magnetic field. (Reprinted from J. P. Ge, Y. X. Hu, T. R. Zhang, and Y. D. Yin, Journal of the American Chemical Society 129: 8974, 2007. With permission.)

with the majority part of the inorganic core engulfed in the poly­mer phase. The high viscosity of the monomer-swollen shell, achieved by introducing a cross-linker of DVB during poly­mer­i­za­tion, limits the transportation of monomers and leads to the formation of a concentric core-shell structure of Fe3O4@SiO2@PS (Figure 3.6b). The spherical symmetry of the external interface can be broken as a result of phase separation when monomer concentration is increased, forming ellipsoidal colloids with a magnetic core eccentrically located at one end. The considerable effects of swelling and phase separation are responsible for the ellipsoidal shape of the colloids. At the early stages of poly­mer­i­za­ tion, the particles have a spherical and concentric morphology similar to that in Figure 3.6b. As the thickness of shell poly­mer increases, more excessive styrene monomers are absorbed into the cross-linked poly­mer networks. In the final stage, the elastic stress driven by the entropy change of the swollen networks causes phase separation of the monomer from the network and eventually forms additional bulges attached to the original particles. As discussed in previous sections, phase separation is negligible when the starting monomer concentration is low so that the final products have a spherical shape. Further increasing the concentration of monomers induces phase separation and forms ellipsoidal particles. When the swelling and phase separation processes are performed in two separate steps, nonspherical colloids can be produced with a higher degree of control over the shape asymmetry. Starting with the cross-linked concentric core-shell particles, a series of nonspherical poly­mer particles with controllable size of the new domains can be prepared by taking advantage of the well-developed swelling and phase separation processes in seeded emulsion poly­mer­i­za­tion, where the relative size of the new domain to the original

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

inorganic sphere changes dramatically as the monomer:seed ratio increases (Figure 3.6c–f). The combination of anisotropic shapes and magnetic properties makes these composite colloids new types of building blocks for constructing secondary structures. The composite spheres with concentric and eccentric superparamagnetic cores display distinct assembly behaviors when they are subjected to an external magnetic field, as shown in Figure 3.6g and h. The concentric particles form simple linear chains, which are expected for building blocks with simple isotropic configurations, while more complicated zigzag chains have been observed when the eccentric particles are assembled under similar conditions. The zigzag configuration is a direct result of the eccentric structure: the strong magnetic dipole interactions that pull the magnetic cores in the neighboring colloids to the closest positions. 3.3.2 Solvent Evaporation and Seeded Dispersion Polymerization The combination of seeded dispersion poly­mer­i­za­tion (SDP) and solvent evaporation represents a unique kinetic-based technique for the preparation of nonspherical poly­mer particles, whose glass transition temperature (Tg) usually exceeds the poly­mer­i­za­tion temperature so that the viscosity within the particles is high enough to prevent equilibrium morphologies from being obtained. Recently, Okubo et al. have developed an SDP method for the preparation of nonspherical particles with the aid of organic solvents (Fujibayashi et al. 2007; Okubo et al. 2002). The solvent molecules are selectively absorbed into certain particle domains, whose volume decreases dramatically as the solvent evaporates after poly­mer­i­za­tion, leading to the formation of golfball-like, polyhedral, and disk-like particles. A typical system involves the SDP of 2-ethylhexyl methacrylate (EHMA) with PS seeds in the presence of various hydrocarbon solvents. The key to controlling the shape of the poly­mer particles lies in the absorption of hydrocarbon solvent into certain domains and their coalescence during the reaction. As the dispersion poly­mer­i­za­tion proceeds, both the PS and PEHMA domain absorb the hydrocarbon solvent, but the PEHMA/solvent domain grows much larger than the PS/solvent domain. The absorption of hydrocarbon solvent significantly increases the particle volume and decreases the viscosity of the poly­mer network, which accelerates the coalescence of the PEHMA/ solvent domain by collision and Ostwald ripening. Thermodynamically, the composite particle prefers to contain as few PEHMA/hydrocarbon domains as possible because the reduction of the interface between PEHMA/solvent and PS phase will decrease the interfacial free energy. However, the practical degree of domain coalescence is always affected by several kinetic considerations, such as the viscosity of the PS/solvent domain and the reaction time. Finally, the solvent evaporates and the PEHMA/solvent domain shrinks to produce nonspherical particles. The degree of coalescence of the PEHMA/ solvent domain determines whether the products are spheres, hemispheres,

77

Advanced Polymer Nanoparticles with Nonspherical Morphologies

(a)

(b)

2 µm (d)

(c)

2 µm (e)

2 µm

2 µm (f )

2 µm

2 µm

Figure 3.7 SEM images of PS particles after extraction of PEHMA and decane, prepared by seeded dispersion poly­mer­i­za­t ion at various conversions of (a) 5%, (b) 13%, (c) 34%, (d) 49%, (e) 57%, and (f) 69%. (Reprinted from T. Fujibayashi and M. Okubo, Langmuir 23: 7958, 2007. With permission.)

golf balls, polyhedra, or disks. Any experimental parameter with influence on the absorption of hydrocarbon and the coalescence of the PEHMA/solvent domain can be used to control the morphology of the nonspherical particles (Fujibayashi et al. 2007; Okubo et al. 2002). Reaction time. Particles with various percent conversions of EHMA collected at different reaction times show dramatically different morphologies (Figure  3.7). Initially, spherical particles with dents are observed after 5% conversion of EHMA. The number of dents on the surface increases as the poly­mer­i­za­tion proceeds, which leads to the formation of golf-ball-like particles at a conversion of 13%. This result can be explained by the increasing number of PEHMA/solvent domains as the EHMA is gradually poly­mer­ ized. The particles then keep on changing their shape to polyhedron at an EHMA conversion of 34 to 57%, as the PEHMA/solvent domains coalesce into several larger domains. Upon further coalescence, the PEHMA/solvent domains eventually combine into two large hemispherical domains at after 69% conversion, leaving a PS disc-like domain sandwiched in between to form a hamburger-like structure. Time-dependent hydrocarbon absorption and domain coalescence have great influence on the particle shapes produced by SDP. Type of hydrocarbon. PS/EHMA composite particles with different shapes can also be synthesized by introducing various hydrocarbon solvents. By

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

decreasing the length of the alkyl chain of the hydrocarbons, the particle shapes change from golf ball (hexadecane) to polyhedron (tetradecane, dodecane), and then to disks (decane, octane, hexane) at the same reaction conditions. Gas chromatography studies indicate that the amount of hydrocarbon absorbed by the PS particles increases in the order of hexadecane, tetradecane, dodecane, decane, octane, and hexane, suggesting that shortchain hydrocarbons have a higher affinity for the PS. DSC heating curves of swollen PS particles also show that the Tg shifts to a lower zone as the alkyl chain length decreases, which means the viscosity of the PS/solvent domain decreases accordingly. For PS particles swollen with short-chain hydrocarbons, both the increased amount of absorbed solvent and decreased viscosity promote the enlargement and coalescence of PEHMA/solvent domains, leading to the shape transformation from golf balls to disks. Methanol:water ratio. The aforementioned conclusions are consistent with the results when particles are prepared in methanol/water solutions with different ratios. A high methanol:water ratio (90:10 w/w) enhances the absorption of hydrocarbons so that a disk is the preferential shape. On the other hand, a low methanol:water ratio (70:30 w/w) leads to polyhedral particles. Amount of solvents. The influence of the amount of solvent has been investigated through a different reaction system, where particles are prepared by the SDP of poly(methyl methacrylate) (PMMA) seeds, styrene, and decalin (solvent droplet) in a mixture of methanol and water. In this case, all the particles are golf-ball-like and no transformation to disks is observed, probably due to thermodynamic reasons for the specific domains of PMMA/ decalin and PS/decalin. By increasing the decalin, the number of surface dents decreases, and the domains enlarge by the coalescence of neighboring domains. This result is consistent with the expectation that increasing the amount of solvent will enhance the solvent absorption and domain coalescence, making the dents on the golf balls fewer in number but larger in size.

3.4 Physical Posttreatment Approaches In addition to direct chemical synthesis, indirect approaches by posttreatment of preexisting structures have also been widely used to prepare particles with complex nonspherical shapes, including those that are usually inaccessible by direct methods. Spherical poly­mer particles are usually synthesized first using chemical methods such as emulsion poly­mer­i­za­tion, and then posttransformed into nonspherical structures by either physical or chemical means such as stretching and self-assembly (Champion et al. 2007; Courbaron et al. 2007; Hu et al. 2008; Jiang et al. 2001).

Advanced Polymer Nanoparticles with Nonspherical Morphologies

79

3.4.1 Stretching 3.4.1.1 Simple 1D Stretching The most straightforward indirect method involves one-dimensional (1D) physical deformation of poly­mer nanoparticles embedded in polymeric matrices at elevated temperatures. It was first developed by Felder while stretching a polyvinyl alcohol (PVA) film to produce monodisperse ellipsoidal dye-containing polyvinyl acetate microparticles embedded in the matrix (Felder 1966, 1968). Figure  3.8 shows the schematic procedure of this indirect method that employs uniaxial viscoelastic deformation to convert colloidal particles from spherical to ellipsoidal shapes (Keville et al. 1991). In this method, monodisperse, spherical particles of a poly­ mer—for example, PS, PMMA, and poly(vinyl toluene)—are first dispersed in a precursor solution of elastic matrix such as PVA or un-cross-linked poly(dimethylsiloxane) PDMS. An elastic film is formed after solvent evaporation or poly­mer­i­za­t ion of the matrix solution. By stretching the film at a temperature higher than the Tg of the poly­mer latexes, spherical particles can be transformed into uniform ellipsoids. The softened poly­mer spheres deform in the elongated matrix film and become ellipsoids whose aspect ratio can be controlled by changing the magnitude of uniaxial elongation and the ratio between the elastic moduli of the matrix and the poly­mer spheres (Ho et al. 1993). In the case of PS particles in PVA, the particle deformation is enabled by the strong adhesion arising from the hydrogen bond between the hydroxyl groups on the PVA and the surface groups on the PVA PS

M

at

rix

di

ss

ol

ut

io

n

St re tch

Figure 3.8 Schematic illustration of stretching polyvinyl alcohol films with embedded particles.

80

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

latex particle surface (Champion et al. 2007; Ho et al. 1993). The ellipsoidal shape resulting from the viscoelastic deformation can be completely retained by cooling down the sample below the Tg of the poly­mer sphere, while the matrix remains constrained in the elongated state. These ellipsoidal particles can then be collected as a stable dispersion by dissolving the matrix with an appropriate solvent. To obtain well-defined microspheroids, the poly­mer particles should possess good chemical and physical stability to be able to withstand the subsequent heating/solvent treatment and be able to remain colloidally stable in the media used in the various synthesis steps. The matrix, which consists of cross-linked elastomer or thermoplastics with controlled elastic properties and high ultimate elongation, can determine the maximum aspect ratio of the obtained ellipsoids. The elastic modulus of the matrix can be adjusted by controlling the cross-linking density. With higher cross-linking density, the ultimate elongation is decreased and stress relaxation is less pronounced. A number of thermoplastics or elastomers have been found to be good elastic matrixes with typical examples including PVA and cross-linked PDMS. The difference between an elastomer and a thermoplastic is that an elastomer tends to relax back to the unstretched state, while a thermoplastic will remain in the stretched state forever once the sample has been cooled. In the ideal case, if the elastic properties of the particles and the matrix are identical and the materials are pure elastic, the aspect ratio could be predicted by using the equation suggested by Eshelby et al.: 3

1 = (1 + e) 2 , d



(3.3)

where l is the length of the major axis of the spheroid, d is the diameter of its cross section normal to the axis, and e is the axial strain e=(l-l0)/l0 (Eshelby et al. 1957). If the elastic properties of the particles are not identical to that of the matrix, the resulting aspect ratio will also depend on the ratio of elastic moduli, which will be predicted as



1 = d

  1 1+     = 0.4(1 − r ) 

e

1   1 + (1 + e) 2 − 1 1 − 0.4(1 − r )  

,

(3.4)

where r is the moduli ratio, r=G1/G, and G and G1 are the elastic moduli of the matrix and the particles. For matrix materials with nonlinear elastic or viscoelastic properties, or when contribution of interfacial energy is significant, the aspect ratio will deviate from the predictions. Moreover, it should be

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taken into account that the properties of the matrix embedded with poly­mer nanoparticles might be different from those of the pure material. The final shape of the poly­mer particles depends on a few key parameters, including the thickness of the film, the viscosity of a liquefied droplet, and the temperature. A practical problem of this simple stretching approach is that the uniaxial stretching is not always uniform throughout the whole film due to the formation and propagation of necks at the center of the poly­mer strip. To improve the uniformity of the recovered particles, strips of the film around the center with lengths corresponding to the expected draw ratio are cut out from the film and used for recovery of the particles. This indirect 1D deformation approach has been investigated by a number of research groups for generating small quantities of micrometer-sized ellipsoids of polymers for light scattering, rheological, or other fundamental studies. Ellipsoidal PS particles of a few micrometers with predesigned axial ratios were reported by Nagy and Keller through the affine deformation of uniform spherical PS beads in a deformable matrix (Ho et al. 1993). PMMA spheroids produced by deforming an elastic matrix of PDMS were later fully studied by Keville et al. (1991). Lu et al. (2002) also exploited the use of this method in generating long-range ordered three-dimensional (3D) colloidal crystals with poly­mer ellipsoids as building blocks. Xu et al. (2007) prepared hollow ellipsoids with desired aspect ratios by stretching a PVA film embedded with PS hollow spheres. The hollow ellipsoids can be used further as templates for the synthesis of composite ellipsoids. 3.4.1.2 Modified Stretching Scheme The 1D stretching scheme outlined previously allows only for the production of simple ellipsoidal particles. Modification of the stretching/heating sequence or using a liquefaction method makes it possible to produce particles with highly complex shapes. As demonstrated by Champion et al. (2007) in their recent reports, this modified stretching protocol can be used to generate particles of more than 20 distinct shapes including ellipsoids with flat ends, rods with circular cross section, rec­tangular disks, and sharp-ended worm-like particles. Figure 3.9 shows the general procedure, which can be categorized into two schemes. The first modification involves the liquefaction of particles by using toluene instead of heating, and then solidification by solvent evaporation after stretching. As indicated previously, the particle viscosity is a critical parameter that dictates whether a deformed particle will have pointed or flat ends and whether the original width is preserved. Since the liquefaction of the particles using toluene leads to a much lower viscosity than when they are heated under otherwise similar conditions, it is possible to produce nonspherical particles with different shapes. With 1D stretching under this condition,

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Scheme A

Liquefy

Stretch

Solidify

Stretch

Liquefy

Solidify

Scheme B

Figure 3.9 Methods used for making particles with different shapes can be categorized into two general schemes. (Reprinted from J. A. Champion, Y. K. Katare, and S. Mitragotri, Proceedings of the National Academy of Sciences of the United States of America 104: 11901, 2007. With permission.)

thin elliptical disks with curved ends can be obtained, while flat circular disks can be fabricated with two-dimensional (2D) stretching. The second modification involves changing the stretching/heating sequence. In this case, the elastic matrix embedded with particles is first deformed so that voids are created around the particles. Liquefaction of the particles by controlled heating above the Tg in the presence of voids allows the production of many additional complex shapes (Figure 3.10). During lique­ faction, softened PS will fill the voids by wetting the film (Figure 3.10e–f). At low liquefying temperature (~130°C), the high viscosity of PS inhibits complete filling of the voids and leads to barrel-like particles. At higher temperatures (~140°C), PS wets the PVA matrix better due to its decreased viscosity, and leads to the filling of one end of the void, eventually forming bullet-like structures. Moreover, by liquefying the PS particles with toluene, more different shapes will be formed as a result of the even lower viscosity: conducting 1D stretching in air can produce pill-like particles while moderate 2D stretching leads to pulley shapes. More extensive stretching forms biconvex lenses. The combination and/or repetition of multiple steps of stretching, heating, and toluene liquefaction can lead to even more unusual shapes including ribbon-like particles with curled ends, bicone, diamond disks, emarginated disks, flat pills, elongated hexagonal disks, ravioli, and tacos (Figure 3.10g–h). With further modification of the surface texture by relaxing the stretched

Advanced Polymer Nanoparticles with Nonspherical Morphologies

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

83

Figure 3.10 SEM images of shapes made by using (a–d) scheme A; (e–f) scheme B; (g–h) a combination of schemes A and B. (Adapted from J. A. Champion, Y. K. Katare, and S. Mitragotri, Proceedings of the National Academy of Sciences of the United States of America 104: 11901, 2007. With permission.)

film ahead of liquefaction, wrinkled prolate ellipsoids, wrinkled oblate ellipsoids, and porous elliptical disks can be formed. 3.4.1.3 2D Stretching While the majority of works involve simple uniaxial stretching, which yields prolate ellipsoids with defined aspect ratios, only a few reports have explored the possibility of the deformation of spheres using 2D stretching. As demonstrated by Champion et al. (2007), a 2D stretching method produces oblate shapes that are difficult to realize in the 1D stretching scheme. Since biaxial stretching with orthogonal forces may lead to nonuniform deformation of the film, particularly at high stretching ratios, few reports have detailed the possibility of the uniform deformation of spheres into well-controlled diskshaped structures. A simple blown film process has been developed that can uniformly deform poly­mer spheres across the blown film and allows the fabrication of disk-shaped ellipsoids with good control (Hu et al. 2008).

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Oil bath

PS/PVA film

PS oblate spherioids

PS spheres

Figure 3.11 Schematic outline of the blown film process. (Reprinted from Y. X. Hu, J. P. Ge, T. R. Zhang, and Y. D. Yin, Advanced Materials 20: 4599, 2008. With permission.)

Figure 3.11 schematically outlines the procedure. A thin composite PS/PVA film is first prepared and then mounted on top of the wide opening of a ceramic filtering funnel, and sealed with a steel clamp. The system is then immersed into a silicon oil bath preheated at 160°C. As this composite film softens and becomes deformable at this temperature, air is then injected into the funnel through the small opening using a syringe, allowing the film to blow into a dome-like shape. The funnel is removed from the oil bath and cooled in air with the pressure maintained so that the stretched PVA film does not show apparent shrinkage upon cooling. The liquefied PS particles experience a uniform 2D stretching force because of their small sizes compared to the PVA film, and eventually evolve into disk shapes during the bubble expansion. The transformation from spheres to disks can be controlled by the extent of bubble expansion, which can be represented simply by the ratio of the height of the bubble (H) to the original film size (D). Practically, the height of the bubble can be controlled by the amount of air injected into the funnel. Figure 3.12 shows that the major axis of the disks increases dramatically with the degree of expansion of the film (H/D). By assuming that both the particle and the matrix materials are purely elastic with identical elastic properties, a sphere will deform into a disk-shaped ellipsoid under biaxial tension by following the relation of

Rd R0 = 2

H D

.

Here Rd is the major axis of the disks, R0 the radius of the original spheres, H the height of the bubble, and D the original film diameter. In fact, the length of the major axis increases with the degree of bubble expansion at a

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(e) 2.2 2.0 1.8 1.6 1.4 1.2 1.0

b

Rd/Ro

a

0.0 c

d

0.2 0.4 H/D

Figure 3.12 (a) SEM image of the starting PS spheres. SEM images of PS disks with controllable diameters by injecting different amounts of air: (b) 716 nm; (c) 903 nm; (d) 1149 nm; (e) the stretching ratio Rd:R0 of PS disks as a function of the degree of bubble expansion (H/D). The insets in b–d show a gradual decrease in the minor axis during the stretching. Scale bars in insets are 500 nm and the others are 1 mm. (Reprinted from Y. X. Hu, J. P. Ge, T. R. Zhang, and Y. D. Yin, Advanced Materials 20: 4599, 2008. With permission.)

rate higher than the value predicted with this simple model, which could result from the viscoelastic nature of the materials, the difference in elastic moduli between the particles and the matrix, and the interfacial energy contribution. The blown film process can also be applied to transform nanoparticle­embedded poly­mer spheres into disk-shaped composite structures. Typ­i­ cally, the nanoparticles are dispersed in the poly­mer spheres without strong interactions between each other. As a result, they can move with the hydrodynamic flow during the transformation of the poly­mer particles. We have prepared magnetic microdisks using iron oxide–doped PS beads as the starting materials, and demonstrated the manipulation of their spatial orientation by using external magnetic fields. More complex structures can be achieved by stretching colloidal spheres containing multiple components with different elastic properties. For example, flying saucer–shaped particles can be produced when SiO2@PS core-shell composite particles are used

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(a)

(b)

(c)

(d)

Figure 3.13 TEM images of flying saucers (a) without magnetic core; (c) with magnetic core; SEM images of (b) flying saucers and (d) hollow disk-shaped PS. (Images (a) and (b) adapted from Y. X. Hu, J. P. Ge, T. R. Zhang, and Y. D. Yin, Advanced Materials 20: 4599, 2008. With permission.)

as the starting materials (Figure 3.13). When such core-shell composite colloids are ­subjected to blown film stretching, only the PS shell can be deformed into disks. The silica core remains spherical because of its rigid nature. As a result of the good adhesion between the PS and the silica surface, the original spherical core-shell particles are transformed into flying saucers with a thin poly­mer layer covering silica. If anisotropic composite particles are used as the starting materials, more geometrically complex structures can be fabricated through this blown film process. In addition, by incorporating active materials such as magnetic particles to the silica cores or using hollow poly­mer particles, it is possible to produce multifunctional colloids with complex shapes for various new applications (Figure 3.13c–d). 3.4.2 Compression In principle, a thin elastic film containing poly­mer particles can also be deformed by mechanical compression. However, such efforts have been rarely reported probably because of the requirement for a high uniformity in film thickness and pressing force in order to obtain uniform deformation. Nevertheless, literature still contains some elegant works that utilize mechanical compression for nonspherical particle fabrication. For example, Sun et al. (2005) recently reported the use of thermal pressing of colloidal crystals for preparing nonspherical particles with well-defined shapes such

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as polyhedrons. In this case, a crystalline array of monodispersed poly­ mer particles is sandwiched between two solid substrates and then compressed while heating the system at a temperature slightly lower than the Tg of the poly­mer. Heating at this temperature allows the softening of poly­ mer chains to facilitate particle deformation upon pressing, and at the same time prevents the colloidal crystals from fusing into continuous films. After the thermal pressing treatment, the spherical particles are transformed into polyhedrons in accordance to the structure of the colloidal crystal, and the long-range order of the 3D lattice is essentially preserved (Figure  3.14). In addition to the shape change of the poly­mer particles, the thermal pressing also leads to obvious changes in the optical properties of colloidal crystals. Another method that involves mechanical compression was reported by Courbaron et al. (2007), who produced disk-shaped poly­mer particles by compressing an elastic aqueous gel containing oil-in-water emulsion droplets. An emulsion containing various polymerizable oil droplets is first mixed with a hot solution of two polysaccharides. By lowering the temperature below the gelling point of the polysaccharide solution, the continuous phase of the emulsion becomes a gel and acquires the elastic properties. Upon compression, the emulsion droplets of polymerizable oil are deformed due to the local strain caused by the macroscopic stress applied to the gel. UV irradiation initiates the poly­mer­i­za­tion of the emulsion droplets and produces solid poly­mer particles. Heating the sample above 80°C melts the gel and releases the solid disk-shaped particles. Ellipsoids of a variety of poly­mer materials can be obtained by incorporating different polymerizable precursors inside the emulsion droplets. However, the particles are highly polydisperse due to the inhomogeneous nature of emulsion droplets. Another limit of this process is the difficulty in achieving higher aspect ratios as the gel ruptures easily when the elongation ratio is above 1.55. 3.4.3 Self-Assembly Besides posttreatment approaches that involve physical deformation, selfassembly represents another type of method that can produce poly­mer particles with complex structures. Generally speaking, these self-assembly methods always start with presynthesized uniform poly­mer particles and then use templates as physical confinement to assemble a limited number of particles into the desired geometric structures. Two types of templates have been used in the self-assembly processes: one variety is soft templates such as droplets in an emulsion system, and the other is hard templates such as patterned thin photo resist films. 3.4.3.1 Self-Assembly in Soft Templates In this method, a three-phase emulsion system is employed to form complex-shaped aggregates of colloidal particles (Velev et al. 2000). Suspended

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A)

(a)

(b)

(d)

Evaporation

(c)

B)

Thermalpressing

(a)

(b)

1 µm (c)

250 nm (d)

1 µm

250 nm

Figure 3.14 A: Schematic illustration of the procedure used to prepare NSCCs. B: (a) Morphology of the CCs fabricated by two substrate vertical deposition. (b–d) Typical SEM images of the NSCCs. (Images adapted from Z. Q. Sun, X. Chen, J. H. Zhang, Z. M. Chen, K. Zhang, X. Yan, Y. F. Wang, W. Z. Yu, and B. Yang, Langmuir 21: 8987, 2005. With permission.)

emulsion droplets are used as templates within which the colloidal particles such as polymers can be gradually concentrated by drying to form aggregates with unique packings, yielding different kinds of microstructured asymmetric assemblies (Yi et al. 2002, 2004; Cho et al. 2005a, 2005b). The shapes of the as-synthesized anisotropic clusters can be controlled by the

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size of suspended template droplets, the number of colloids per droplet, and the surface properties of the colloidal particles. Moreover, composite assemblies can be achieved by varying the components of the colloidal beads. This soft-template approach involving encapsulation and shrinkage is efficient at creating polymeric clusters containing a small number of spheres (n = ~12–15) and is a high-throughput method capable of producing a massive number of clusters, approximately 108–1010 in lab-scale experiments. The method was first reported by Manoharan et al. in 2003, and involves poly­ mer particles such as PS dispersed in an oil-in-water emulsion system with each oil droplet containing a small number (N) of spheres. By preferentially removing the liquid from a droplet containing particles absorbed onto its surface or confined in its core, compact clusters with different shapes can be obtained as a result of capillary forces and Van der Waals interactions during the drying process. Interestingly, the final particle packings are unique for all N < 11 and correspond to the clusters with minimized second moments of mass distribution, M = ∑i(ri–r0)2 (r0 is the center of mass of the cluster). Subsequently, clusters of different aggregation numbers are fractionated by density gradient centrifugation. However, this method lacks control of the emulsification conditions, leading to polydisperse emulsions and severely limited yields of different types of clusters. Since the size of the emulsion droplet is one of the crucial factors that determine the final shape of the poly­mer clusters, extensive research has been conducted to generate uniform emulsion droplets. A series of novel emulsification strategies have been exploited, including for example microfluidic devices, micropipette injection, and electrospray. All of these methods involve a droplet break-off technique to produce monodispersed droplets (Umbanhowar et al. 2000). The size of droplets detaching from a tip immersed in a coflowing stream has already been investigated (Yi et al. 2004). When the flow rate in the capillary is low, a balance between the interfacial tension and the drag force on the droplet at the end of the tip results in a droplet diameter dd given by

 γ  dd = dti 1 + ,  3µηc 

(3.5)

where dti is the inner diameter of the capillary tip, γ the interfacial tension between the water and oil, ηc the viscosity of the continuous phase, and µ the velocity of the continuous phase (the shear rate). The droplet sizes of oilin-water emulsions increases when the viscosity ratio between the continuous and dispersed phases is increased because their high internal viscosity resists fragmentation. Also, a low to moderate shear rate can generate the highest proportions of aggregates containing a small number of particles. In

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all, by controlling various parameters, droplets with different sizes can be obtained, thus generating different packing numbers in the emulsion template assisted assembly. The surface properties of these particles cannot be neglected when controlling the structures of the packings. The particles inside the droplets pack according to the capillary force acting upon them. The geometrical structure of clusters can be predicted as a function of constituent particle number through theoretical considerations of minimizing Lennard-Jones potential, second moment of the mass distribution, or Coulomb potential (Cho et al. 2005). By optimizing these functions respectively, three types of sphere packings or cluster structures have been proposed (Livshits et al. 1999; Maranas et al. 1992; Sloane et al. 1995; Wille 1986). The configurations of clusters predicted by the three models remain the same when the packing number is smaller than seven. When a large number of particles are assembled, the structure is sensitive to small differences in the interparticle forces, and therefore various configurations of clusters can be achieved when particles with different surface properties are used and consequently different particle interactions are involved. For example, it has been reported that 11 PS clusters assemble into a nonconvex structure in oil while the same number of PMMA spheres pack in a convex shape (Yi et al. 2004). The different packing behavior is attributed to the different swelling characteristics of these two types of particles. The van der Waals attraction, which varies between systems, also contributes to the structure determination in the assembly of large number particles by fixing them at different points in the consolidation process before all of the oil evaporates. Overall, the packing constraints imposed by the particle interaction and the inward pressure of the shrinking oil droplets determine the final configurations when a large number of particles are considered. Apparently, the number of spheres per droplet is another important parameter, which can be easily adjusted by controlling the volume fraction of poly­mer particles in the oil phase (Zerrouki et al. 2006). Largervolume fractions of the particles in the oil phase will result in anisotropic clusters with higher packing numbers while smaller-volume fractions generate clusters with lower packing numbers. Further control of the complex composite assemblies can be attained by controlling the original drop components, for example, by mixing two or more different types of particles (Cho et al. 2005a, 2005b; Reculusa et al. 2004; Rabideau et al. 2004). The segregation of two types of colloids with different sizes and physical properties during assembly yields complex anisotropic particles. For example, with a mixture of regular PS beads and paramagnetic particles, anisotropic particles can be produced by gravitational separation of these components or by the application of a constant magnetic field (Rabideau et al. 2004). Suspensions containing large latex particles (~270 nm) and small gold particles can form unconventional “glazed doughnut” shapes during the drying (Velev et al. 2000).

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3.4.3.2 Self-Assembly in Hard Template The soft-template method can create nonspherical complex assemblies in relatively large quantities. However, more effort is still needed to control the uniformity of the size and structural arrangement of the assemblies. By using hard templates that are lithographically patterned with designed shapes, homogeneous complex aggregates (such as polygonal and polyhedral clusters) assembled from monodispersed spherical colloids can be obtained with well-controlled sizes and near identical structures (Yin et al. 2001a, 2001b). Figure  3.15 outlines the schematic procedure of self-assembly with designed hard templates. The key strategy of this assembly approach is the dewetting of an aqueous dispersion of monodispersed spherical colloidal particles across a surface that contains template holes. As shown schematically in Figure 3.15a, the assembly is performed in a glass cell, which is composed of two glass substrates. The surface of the bottom substrate contains a 2D array of cylindrical holes lithographically patterned in a thin film of photo resist. When the particle dispersion is allowed to dewet slowly across the cell, the capillary force exerted on the rear edge of this liquid slug drags the spher­ical particles across the surface of the bottom substrate until they are physically trapped in the arrays of cylindrical holes. The structural arrangement of these beads can be controlled by the maximum number of poly­mer beads that can be possibly retained in each hole, which can be determined by the ratios between the dimensions (diameter and height) of the holes and the diameter of the poly­mer beads. A range of uniform, polygonal or poly­ hedral clusters can be formed in such 2D arrays of holes. When the solvent is

(a)

Gla

Water

Fe

Flow

(b)

c(c)

(d)

(e)

ss on

cti dire

Fc Fg Patterned photoresist

2 µm

Figure 3.15 (a) Schematic illustration of the procedure to assemble spherical colloids into well-controlled clusters under the physical confinement exerted by a 2D array of cylindrical holes patterned in a thin film of photo resist. The size, shape, and structure of these clusters can all be easily controlled by changing the ratios between the dimensions of the holes and the diameter of the poly­mer beads. (b–e) SEM images of dimers, trimers, squares, and pentamers formed in photo resist templates.

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completely evaporated, the poly­mer beads trapped in each hole always tend toward physical contact as a result of attractive capillary forces among them. Once the solvent is evaporated, clusters in each hole can be welded into a permanent form via thermal treatment at a temperature slightly higher than the glass transition temperature of the poly­mer. The extent of viscoelastic deformation of colloidal beads during thermal jointing depends on a number of parameters, in particular, the Tg of the beads. The anisotropic clusters such as dimers, trimers, or squares of PS beads can then be released by dissolving the photo resist film with ethanol under sonication. This self-assembly approach can be conveniently extended to the generation of asymmetric dimers from two types of monodispersed, spherical colloids that could be different in size, chemical composition, surface functionality, density or sign of surface charges, bulk properties, or a combination of characteristics (Yin et al., 2001a). Templates other than cylindrical holes have also been demonstrated to generate aggregates of spherical colloids with more complex geometric shapes and internal configurations (Yin et al. 2001a, 2001b; Xia et al., 2003).

3.5 Summary In this chapter, we have discussed the preparation of nonspherical poly­mer nanoparticles through either direct seeded poly­mer­i­za­tion or indirect posttreatment. Nonspherical particles with relatively simple structures can be prepared by controlling the swelling and phase separation processes in seeded poly­mer­i­za­tion procedures, while more complicated anisotropic polymeric particles can be obtained through indirect approaches such as the stretching of a matrix embedded with poly­mer particles. Self-assembly processes, as one type of unique posttreatment approach, do not rely on any physical or chemical deformation techniques; instead, they involve using templates to organize the precursor nanoparticles into secondary structures. The starting materials used in the indirect approaches are not necessarily limited to spherical particles. For example, nonspherical particles obtained by seeded emulsion poly­mer­i­za­tion might also be employed as precursors to fabricate even more complicated structures through self-assembly. Nonspherical poly­ mer nanoparticles can be used as interesting model systems for studying the behavior of molecules in solution, or modeling the behavior of irregular colloidal particles that can be found everywhere in our daily lives. They also have great potential in a wide range of technological applications including the fabrication of three-dimensional photonic colloidal crystals.

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Velev, O. D., Lenhoff, A. M., and E. W. Kaler. 2000. A class of microstructured particles through colloidal crystallization. Science 287:2240–43. Whitby, G. S., and M. Katz. 1933. Synthetic rubber. Industrial and Engineering Chemistry 25:1204–1210. Wille, L. T. 1986. Searching potential energy surfaces by simulated annealing. Nature 324:46–48. Xia, Y. N., Gates, B., Yin, Y. D., and Y. Lu. 2000. Monodispersed colloidal spheres. Old materials with new applications. Advanced Materials 12:693–713. Yin, Y. D., Lu, Y., Gates, B., and Y. N. Xia. 2003. Template-assisted self-assembly of spherical colloids into complex and controllable structures. Advanced Functional Materials 13:907–18. Xu, C., Wang, Q., Xu, H., Xie, S., and Z. Yang. 2007. General synthesis of hollow composite ellipsoids. Colloid and Polymer Science 285:1471–78. Yi, G. R., Manoharan, V. N., Klein, S., Brzezinska, K. R., Pine, D. J., Lange, F. F., and S. M. Yang. 2002. Monodisperse micrometer-scale spherical assemblies of poly­ mer particles. Advanced Materials 14:1137–40. Yi, G. R., Manoharan, V. N., Michel, E., Elsesser, M. T., Yang, S. M., and D. J. Pine. 2004. Colloidal clusters of silica or poly­mer microspheres. Advanced Materials 16:1204–8. Yin, Y. D., Lu, Y., Gates, B., and Y. N. Xia. 2001. Template-assisted self-assembly: A practical route to complex aggregates of monodispersed colloids with welldefined sizes, shapes, and structures. Journal of the American Chemical Society 123:8718–29. Yin, Y. D., Lu, Y., and Y. N. Xia. 2001a. A self-assembly approach to the formation of asymmetric dimers from monodispersed spherical colloids. Journal of the American Chemical Society 123: 771–72. ———. 2001b. Self-assembly of monodispersed spherical colloids into 1D chains with well-defined lengths and structures. Journal of Material Chemistry 11:987–89. Yin, Y. D., and Y. N. Xia. 2001. Self-assembly of monodispersed spherical colloids into complex aggregates with well-defined sizes, shapes, and structures. Advanced Materials 13:267–71. Zerrouki, D., B. Rotenberg, S. Abramson, J. Baudry, C. Goubault, F. Leal-Calderon, D. J. Pine, and J. Bibette. 2006. Preparation of doublet, triangular, and tetrahedral colloidal clusters by controlled emulsification. Langmuir 22:57–62.

4 Block, Graft, Star, and Gradient Copolymer Particles H. Matahwa, E. T. A. van den Dungen, J. B. McLeary, and B. Klumperman Contents 4.1 Introduction................................................................................................... 98 4.2 Polymerization Techniques for Complex Macromolecular Architectures................................................................................................. 99 4.2.1 Block Copolymer Topology........................................................... 100 4.2.2 Graft Copolymer Topology........................................................... 101 4.2.3 Star Copolymer Topology.............................................................. 103 4.2.4 Gradient Copolymer Topology..................................................... 103 4.3 Polymer Nanoparticles in Heterogeneous Polymerization.................. 104 4.3.1 Approaches for Successful Application of CRP in Heterogeneous Media.................................................................... 105 4.3.2 Challenges with the Application of CRP in Heterogeneous Media................................................................................................ 107 4.3.3 Characteristics of the Individual CRP Techniques in Miniemulsion Polymerization...................................................... 108 4.3.4 Nanoparticles with Complex Architecture Synthesized via CRP in (Mini)emulsion.................................................................. 110 4.4 Polymer Nanoparticles via Self-Assembly.............................................. 113 4.4.1 Synthesis of Amphiphilic Copolymers........................................ 113 4.4.2 Nanostructures via Self-Assembly of Copolymers.................... 114 4.4.3 Nanoparticles Synthesis by Cross-Linking of SelfAssembled Structures.................................................................... 115 4.4.4 Functionalization of Cross-Linked Micelles............................... 121 4.4.5 Potential Applications of Cross-Linked Nanoparticles............. 121 4.5 Conclusions.................................................................................................. 123 References.............................................................................................................. 124

97

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

4.1 Introduction This chapter describes routes that have been utilized in the synthesis of advanced poly­mer nanoparticles. The progress that has been made in the field of controlled radical poly­mer­i­za­tion (CRP) for the synthesis of nanoparticles consisting of advanced topology and morphology is highlighted. Advanced poly­mer topologies that will be discussed include block, graft, star, and gradient copolymers (Scheme 4.1). Heterogeneous poly­mer­i­za­tion techniques are most commonly used to synthesize poly­mer nanoparticles. Polymerization in heterogeneous media is relatively simple and high rates of poly­mer­i­za­tion are obtained, leading to high conversions and high molecular weight polymers in relatively short times. Latex polymers are predominantly synthesized via a free radical poly­mer­i­za­ tion mechanism. This leads to a wide variety of latex products with a large variation of physical and mechanical properties. Polymerizations in heterogeneous media, where the continuous medium is water, provide an environmentally friendly approach for the synthesis of materials, which is necessary due to the increasing restrictions for solvent-based systems. Because water is the medium in which the poly­mer­i­za­tion takes place, easy removal of exothermic reaction heat is facilitated and the final latex is a low-viscosity, easy-to-handle product.

AB diblock copolymer

A-B graft copolymer A-B star copolymer

A-BC heterograft copolymer

A-B gradient copolymer

A-BC miktoarm star copolymer

Scheme 4.1 Various topologies that can be obtained via the employment of various CRP techniques in homogeneous and heterogeneous media. The synthesis of nanoparticles consisting of these topologies is discussed in this chapter.

Block, Graft, Star, and Gradient Copolymer Particles

99

The successful application of CRP techniques in heterogeneous poly­mer­i­ za­tion would provide better control over the molecular weight and give narrow molecular weight distribution polymers. More importantly, due to the retention of the mediating agent as an end group at the poly­mer chain end, the synthesis of (co)polymers comprising advanced macromolecular architectures, such as shown in Scheme 4.1, is easily obtained. Synthesis of poly­mer nanoparticles via self-assembly and cross-linking of amphiphilic copolymers, and their modification for various applications are also discussed. Several approaches to achieving self-assembly of complex architectures can be used. Amphiphilic copolymers can readily self-assemble into nanostructures when a common solvent is replaced by a selective solvent. Additionally, response to stimuli (temperature, pH, or ionic strength) can be used to drive self-assembly of the copolymers. The stable nano­ particles are then obtained by cross-linking of the self-assembled nanostructures. Various chemistries for modification of the nanoparticles and possible applications are highlighted. Advantages, disadvantages, and the feasibility of the various approaches for industrial application are also discussed.

4.2 Polymerization Techniques for Complex Macromolecular Architectures The invention of so-called CRP techniques provided similar flexibility as observed in conventional free radical poly­mer­i­za­tion, but with additional advantages such as control over molecular weight and molecular weight distribution and the ability to easily synthesize structures of complex architecture [1–3]. This is attributed to the long lifetime of the poly­mer chains, which grow throughout the reaction. The poly­mer chains are initiated fast at the early stages of the poly­mer­i­za­tion, and all poly­mer chains grow simultaneously throughout the course of poly­mer­i­za­tion. Due to the involvement of the poly­mer chains in a reversible activation-deactivation mechanism, the majority of poly­mer chains are in a dormant state at any given instant. This means that the active propagating radical concentration is low and that between each activation-deactivation cycle, only a few monomer units are incorporated in the chain. The low active propagating radical concentration also leads to a significantly reduced rate of termination and consequently formation of dead chains. In conventional free radical poly­mer­i­za­tion, all poly­mer chains synthesized are involved in termination reactions leading to so-called “dead” poly­mer chains that are not capable of further growth. In CRP on the other hand, at the end of poly­mer­i­za­tion the poly­mer chains are end-capped with an activator that allows chain extension for the synthesis of structures with complex topology (Scheme 4.1).

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

NMP

O

kact

N

Pn•

kdeact

Pn

O• N

+

kp M

kact ATRP

Pn—X

Mnt —X/L

+

kdeact

Mn+1 t X2/L

+

P n• kp M

RAFT-mediated polymerization

P n• kp

+

Pm

S S Z

kdeact kact

M

Pn

S

• C

S

Z chain-transfer

Pm

kdeact kact

Pm• kp

+

Pn

S S Z

M

Scheme 4.2 Reversible termination mechanism for NMP and ATRP and degenerative transfer mechanism for RAFT-mediated poly­mer­i­za­t ion.

The three main CRP techniques that are employed in poly­mer science nowadays are nitroxide-mediated poly­mer­i­za­tion (NMP), atom transfer radical poly­mer­i­za­tion (ATRP) [4,5], and reversible addition-fragmentation chain transfer (RAFT)-mediated poly­mer­i­za­tion [6,7]. NMP and ATRP are examples of reversible termination, whereas RAFT-mediated poly­mer­i­za­ tion is an example of degenerative transfer (reversible chain-transfer), as illustrated in Scheme 4.2. Both NMP and ATRP are controlled by the persistent radical effect (PRE), which means that every radical-radical termination event leads to an irreversible accumulation of deactivator, shifting the equilibrium toward the dormant species and consequently decreasing the rate of termination. RAFT-mediated poly­mer­i­za­tion requires a conventional radical initiator to start poly­mer­i­za­tion, whereas both ATRP and NMP are self-initiating poly­mer­i­za­tion techniques that initiate poly­mer­i­za­tion via a halogen-containing ATRP initiator or an alkoxyamine, respectively. Scheme 4.3 shows examples of RAFT agents, ATRP ligands used in Cu(I)-mediated ATRP, and the nitroxides 2,2,6,6-tetramethylpiperidinyl-1oxy (TEMPO) and N-tert-butyl-N-(1-diethylphosphono-2,2-dimethylpropyl) nitroxide (SG1, also called DEPN). 4.2.1 Block Copolymer Topology CRP results in chains that are end-capped with a mediating agent, and chain extension is possible to form block copolymers by adding another monomer followed by initiation. The formation of homopolymer during chain extension experiments in RAFT-mediated poly­mer­i­za­tion is inevitable and reduces

101

Block, Graft, Star, and Gradient Copolymer Particles

RAFT agents

S

S

CH3

S C

S C

N

CH3 2-cyanoprop-2-yl dithiobenzoate

CH3 cumyl dithiobenzoate

H benzyl dithiobenzoate

O

S N

O

S

S C

OH

S C

O — poly(ethylene-co-butylene)

S PMMA

S

CH3 poly(ethylene-co-butylene) macroRAFT agent

PMMA macroRAFT agent H

CH3 O S C

S

S OH

CH3 S-butyl-S’-2-methylpropanoic acid trithiocarbonate

H

S S H3C H S-butyl-S’-benzyl trithiocarbonate

C18H37 N

N

N

H9C4

tris[(2-pyridyl)methyl]amine (TPMA) C4H9

H9C4

N

2-2'-bipyridine (bpy)

N

N

N

CH3

N,N,N’,N”,N”-pentamethyldiethylenetriamine (PMDETA) NMP mediators

C4H9 O• N

N

CH3

CH3

N bis(2-pyridylmethyl)octadecylamine (BPMODA)

CH3

S

H dibutyl-1,4-phenylenebis(methylene)bistrithiocarbonate

CH3 H3C

N

H

S

S

S

H3C

N

N

S

S H

ATRP ligands

N

H

S

S N

CH3 2-cyanopentanoic acid dithiobenzoate

H3C

S

CH3

N

4,4'-di(5-nonyl)-2,2'-bipyridine (dNbpy)

O

O• N

CH P OC2H5 OC2H5 SG1

TEMPO

Scheme 4.3 RAFT agents, ligands for complexation with Cu catalyst in ATRP, and NMP mediators employed in the various controlled radical poly­mer­i­za­t ion techniques.

the purity of the block copolymer. This leads to formation of block copoly­ mer in conjunction with the formation of homopolymer, which increases the molecular weight distribution of the final product. In addition, chains that do not contain the RAFT moiety as an end group after the synthesis of the first block cannot be chain extended during the synthesis of the second block and therefore will remain as an impurity in the final poly­mer product. In case the monomer conversion during the synthesis of the first block does not reach 100%, chain extension of the first block with a second monomer will lead to a second block consisting of a random copolymer instead of a homopolymer (provided excess monomer is not removed). 4.2.2 Graft Copolymer Topology Graft copolymers are a type of branched copolymer in which the side chains are structurally distinct from the main chain. The side chains can

102

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

extend from poly­mer backbones [8–12] or ([in]organic nanoparticle) surfaces [13–21]. CRP controls the molecular weight and polydispersity index (PDI) of the backbone and the side chains, and either one may consist of a homo­polymer, block, alternating, or random copolymer topology. Three approaches for the synthesis of graft copolymers include “grafting from,” “grafting onto,” and “grafting through” [1,2,10]. “Grafting from” involves the creation of a predetermined number of initiating sites on the poly­mer backbone or surface, and the subsequent poly­mer­i­za­tion from these initiating sites. This technique inevitably leads to the formation of homopolymer impurity, which requires an extra purification step, unless the side chains are poly­mer­ized via ATRP or NMP, which are self-initiating CRP techniques that are exclusively initiated by halogen-containing ATRP initiators or alkoxyamine initiators, respectively. “Grafting onto” involves the covalent attachment of a preformed poly­mer chain onto a poly­mer backbone/ surface via radical reaction or reaction between complementary functional groups. A disadvantage is the low grafting efficiency due to steric hindrance. “Grafting through” involves the poly­mer­i­za­tion of the pendant vinyl groups of a macromonomer. Generally the degree of poly­mer­i­za­tion of the backbone is low due to the low concentration of vinyl groups and the high steric hindrance around the chain end propagating radical. A facile method to synthesize graft copolymers via CRP is to functionalize the repeating units of the poly­mer backbone with a RAFT agent or ATRP initiator (Scheme 4.4) [22]. After poly­mer­i­za­tion of the backbone, graft copolymers can be synthesized via CRP of the side chains. RAFT-mediated poly­mer­i­za­tion allows for two different approaches. The R-group approach Grafting from a surface using Z-group approach in RAFT-mediated polymerization

OH

O

+

Cl

surface

O

S S

pyridine S

O

R

O

S S

S

R

MA

O

S S

R

S

PMA

RAFT agent

Grafting from a polymer backbone via ATRP CH3

H2C

O O OH HEMA

n

ATRP

O

O

Br

pyridine Br

OH PHEMA

n

O

O

O O

n

Br

ATRP styrene O

O

O

Br

O

O

Br Br ATRP initiating site on side chain

PS Br

Scheme 4.4 Synthesis of graft copolymers with the “grafting from” approach via CRP.

Block, Graft, Star, and Gradient Copolymer Particles

103

involves anchoring of the leaving group to the poly­mer backbone from which the chains are grown. Two macroradicals allow for termination of the poly­ mer chains (and cross-linking between side chains) and loss of RAFT agent functionality. The Z-group approach involves anchoring of the stabilizing group to the poly­mer backbone. In this case, the degree of poly­mer­i­za­tion may be limited due to steric hindrance of the side chains in approaching the RAFT moiety close to the backbone. 4.2.3 Star Copolymer Topology Star poly­mer molecules can be defined as macromolecules containing a single branch point from which linear chains emanate. Polymerization techniques such as conventional free radical poly­mer­i­za­tion and anionic poly­mer­i­za­tion have been used to synthesize star polymers. Star polymers are best prepared by coupling of anionic living polymers with multifunctional electrophilic coupling agents. Multifunctional chloromethylated benzene derivatives or multifunctional chlorosilane compounds are often used as the electrophilic coupling reagents. CRP provided another approach for the synthesis of star polymers with control over molecular weight and PDI [23]. The basic requirement for star poly­mer synthesis is a multifunctional molecule (core) that covalently connects multiple poly­mer chains (arms) by either initiating poly­mer growth or linking preformed poly­mer chains through the multifunctional groups of the molecule [24]. The coupling of two (or more) chemically different polymers results in heteroarm star copolymers, which are often referred to as miktoarm star copolymers (Scheme 4.1). The synthesis of star copolymer particles is readily available by adopting multifunctional initiators for the various CRP techniques (Scheme 4.5). The R-group approach for RAFT-mediated poly­mer­i­za­tion results in the formation of homopolymer impurity and star-star coupling [25–27]. A whole range of products is obtained due to either premature termination of growing poly­mer chains or a mixture of branching point molecules from which a different number of poly­mer chains emanate. Star copolymers are also obtained via the synthesis of linear poly­mer chains and subsequent addition of (divinyl) cross-linker at high(er) conversion, as reported for ATRP [2]. 4.2.4 Gradient Copolymer Topology The synthesis of gradient copolymers can generally be carried out via two methods, that is, spontaneous (batch) and forced (M2 feed) gradient copoly­ mer­i­za­tion. The second method is advantageous for monomer pairs with unfavorable reactivity ratios. The formation of a gradient copolymer requires that the concentration ratio of the monomer pair changes during the course of the poly­mer­i­za­tion. A forced gradient copolymer could be obtained when a second monomer is continuously added to the poly­mer­i­za­tion mixture, which contains only the first monomer.

104

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

S Z

S

Z

S

S

S S

Z

R

S Z

Br O Br

O O

S S S

multiple-arm ATRP initiator

Ph

Br

O N

O

O CH3 Br CH3

O CH3

CH3 O

1,1,1-tris(4-(2-bromoisobutyryloxy)-phenyl)ethane (TBiBPE)

O P O

O

O

O

CH3

CH3 O

O

O

Br

O

R

Ph O

O

Br

O

S

N O Br

O

R

multiple-arm RAFT agent (Z-group approach)

O O

O

S S R

S multiple-arm RAFT agent (R-group approach)

S

S

H3C

O

O

N

Ph

N O

O

O

O O N

O

O P

O

n

multiple-arm SG1 initiator

multiple-arm TEMPO initiator

Scheme 4.5 Multifunctional initiators for the synthesis of star copolymers via various CRP techniques.

4.3 Polymer Nanoparticles in Heterogeneous Polymerization Polymerizations in dispersed systems show a higher rate of poly­mer­i­za­tion and a lower viscosity at high conversion than poly­mer­i­za­tions carried out in solution or bulk. Due to the confinement of a radical within one particle (compartmentalization), radical-radical terminations are minimized and high conversions and high molecular weights are obtained in relatively short times. These are advantages that are of particular interest for industrial processes. Emulsion poly­mer­i­za­tion is one of the most important industrial processes via which stable poly­mer latexes are prepared. In most cases, the monomer swollen micelles are transformed into poly­mer particles via a free radical poly­mer­i­za­tion process. Emulsion poly­mer­i­za­tion requires transport of monomer from the droplets to the poly­mer particles. The fact that the primary nucleation mechanism in emulsion poly­mer­i­za­tion is either via micellar nucleation or via homogeneous nucleation (aggregation of insoluble chains in the continuous phase that are stabilized by surfactant molecules) complicates the synthesis of complex structures. These include core-shell particles that show homogeneity in composition throughout the particle size distribution and molecular weight distribution. The main mechanism of nucleation can be shifted to droplet nucleation if the size of the monomer droplets is small enough (large total surface area);

Block, Graft, Star, and Gradient Copolymer Particles

105

thus, monomer droplets could compete with the micelles for an incoming radical [28]. This technique is referred to as miniemulsion poly­mer­i­za­tion, and simplifies the process considerably as no monomer transport through the aqueous phase is required. For an ideal miniemulsion poly­mer­i­za­tion process, all kinetically stabilized monomer droplets are nucleated and are converted into poly­mer particles [29,30]. The disadvantages of miniemulsion are that the oil-in-water emulsion is subjected to sonication and that a (volatile) hydrophobe (e.g., hexadecane) is added to the formulation. This makes the realization of industrial implementation more cumbersome, although it has been shown that very hydrophobic (co)monomers (such as lauryl methacrylate) [31] or polymers (e.g., poly[methyl methacrylate], PMMA) [32] also can be used as effective hydrophobes. This eliminates the necessity of removing the hydrophobe after poly­mer­i­za­tion. Microemulsion is a heterogeneous poly­mer­i­za­tion technique that uses a very high surfactant load for the stabilization of monomer swollen micelles [33]. Typical weight ratios of surfactant to monomer range between 1 and 2.5. The surfactant concentration is well above the critical micelle concentration (CMC), and all monomer resides within these monomer swollen micelles. This eliminates the need for monomer transport through the aqueous phase, which makes latexes obtained from microemulsions (and miniemulsions) particularly suitable for use as seed. The seed latex can be swollen with monomer, and poly­mer­i­za­tion is then carried out via a batch emulsion poly­mer­i­za­tion process. Microemulsions are spontaneously formed and are therefore thermodynamically stable. Micelles that are not nucleated will disintegrate and the surfactant molecules will adsorb onto the surface of the growing latex particles to provide stabilization. Particle sizes obtained in microemulsion typically range between 10 and 50 nanometers. 4.3.1 Approaches for Successful Application of CRP in Heterogeneous Media The introduction of various CRP techniques (NMP, ATRP, and RAFTmediated poly­mer­i­za­tion, Scheme 4.2) opened up the way for the synthesis of poly­mer particles with complex architecture via a radical poly­mer­i­za­tion technique [1,2]. Application of these CRP techniques in heterogeneous media would combine the high rates of poly­mer­i­za­tion obtained in heterogeneous poly­mer­i­za­tion with the control over the poly­mer architecture offered with CRP [34–38]. Several approaches have been reported for successful application of CRP in heterogeneous media: • Microemulsion and miniemulsion poly­mer­i­za­tion • Preparation of a seed latex via micro- or miniemulsion poly­mer­i­ za­tion and swelling of the particles with monomer (polymerization takes place within these seed latex particles via a batch emulsion poly­mer­i­za­tion process)

106

Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

• In situ formation of poly­mer particles via nanoprecipitation • Self-assembly of block copolymers synthesized via CRP in bulk or solution Stable latexes can be synthesized via CRP in microemulsion [33] and miniemulsion [39–42] poly­mer­i­za­tion. Recently successful ab initio batch or semicontinuous (starved–feed) emulsion poly­mer­iz­ a­tion mediated via RAFT [43–48] and NMP [49–53] has been reported. In most cases, surfactant-free conditions were employed. Latex products were obtained without the formation of coagulum and particles that consist of poly­mer chains with complex topology of controlled molecular weight and low PDI. Additionally, these stable latex products could be used as a seed for (continued) poly­mer­ i­za­tion via a batch emulsion process. The advantage then is that the poly­ mer­i­za­tion starts in either Interval 2 or Interval 3, dependent on the presence of monomer droplets, and thus the process of particle nucleation is circumvented. This avoids the transport of the (hydrophobic) mediating agent to the locus of poly­mer­i­za­tion. The seed latexes are often synthesized under dilute conditions, and for this approach low molecular weight oligomers are targeted. Swelling of the poly­mer particles with monomer increases the solid content of the latex, and subsequent poly­mer­i­za­tion is carried out via a batch emulsion process. Nanoprecipitation involves the synthesis of an oligomer via CRP in solution or bulk. The resulting oligomer is dissolved in acetone, for example, and added dropwise to the aqueous surfactant solution. A stable latex is formed and the particles can be swollen with monomer, after which the poly­mer­i­ za­tion can proceed via a batch emulsion poly­mer­i­za­tion process. The formation of monomer droplets during swelling of the poly­mer particles should be avoided, as poly­mer­i­za­tion within the monomer droplets is one of the main causes for significant latex destabilization. An advantage is that the poly­mer particles are formed in situ and that no monomer transport through the aqueous phase is required. This significantly improves the stability of the latex and the control over the molecular weight and PDI, as the mediating agent is present at the locus of poly­mer­i­za­tion. Prescott et al. reported on the successful application of RAFT-mediated poly­mer­i­za­tion using a similar approach [54]. They prepared a polystyrene (PS) emulsion and transported the RAFT agent to the locus of poly­mer­i­za­tion via the acetone transport technique, after which they successfully conducted RAFT-mediated poly­mer­i­za­tion. The drawback of this technique in their case is that the seed was prepared via conventional radical poly­mer­i­za­tion, and hence the latex product also contained uncontrolled poly­mer that could not be chain extended. Similarly, synthesis of amphiphilic block copolymers via CRP in solution or bulk allows for self-assembly of these block copolymers in the aqueous phase [47]. The amphiphilic block copolymers simultaneously act as mediating agent and stabilizing agent, which eliminates the requirement for a

Block, Graft, Star, and Gradient Copolymer Particles

107

low molecular weight surfactant. The self-assembly process can be induced either via the use of a selective solvent (e.g., water) or upon a change in environment, such as pH, temperature, or concentration of electrolyte. Use of a surface active mediating agent also allows for self-assembly in the aqueous phase [43,44]. The resulting micelles can be swollen with monomer via a controlled feed, and the poly­mer­i­za­tion can take place via a semicontinuous emulsion process. The use of a water-soluble monomer, such as (meth) acrylic acid ([M]AA) or 4-vinyl pyridine (4VP), allows for direct synthesis in the aqueous phase, and the resulting oligomer can be used as stabilizer in seeded semicontinuous emulsion for the poly­mer­i­za­tion (chain extension) of a water insoluble monomer [45–51,53]. However, due to interference of the acid group with the catalyst complex, this approach is not suitable for use in ATRP. Protected group chemistry is often used in this case to protect the acid functionality. 4.3.2 Challenges with the Application of CRP in Heterogeneous Media A common problem that had to be dealt with was the exit of small, mediating agent-derived radicals from the monomer droplets into the aqueous phase. An inherent characteristic of CRP is simultaneous growth of the poly­ mer chains throughout the poly­mer­i­za­tion, and therefore slow formation of high molecular weight poly­mer. This could enhance exit of the radicals from the monomer droplets. Additionally, the resulting high concentration of oligomers at the early stage of the poly­mer­i­za­tion could lead to instability of the latex product because oligomers are known to be very effective swelling agents (superswelling) [55]. It should be noted that chain-transfer reactions in conventional free radical poly­mer­i­za­tion in (mini)emulsion also leads to the formation of small radicals, which can either terminate a long poly­mer chain (via short-long termination events) or exit the poly­mer particle. The absence of radicals in the poly­mer particle leads to rate retardation. In addition, partitioning of the mediating agent between the oil and aqueous phases determines the equilibrium concentrations in both phases and can be adequately controlled by using a sufficiently hydrophobic mediating agent. Initial attempts to perform CRP in a (mini)emulsion process were met with difficulties such as colloidal instability and poor control over the molecular weight and PDI [34,35]. The inability to carry out CRP directly in batch emulsion was attributed to negligible transport of the hydrophobic mediating agent from the large monomer droplets to the poly­mer­i­za­tion loci. The resulting latex was characterized by phase separation and coagulation of small droplets, which lead to instability of the final latex product. Therefore, CRP was applied to miniemulsion poly­mer­i­za­tion, which does not require transport of the (hydrophobic) mediating agent. When a rather hydrophilic mediating agent was used, the early stage of the poly­mer­i­za­tion was characterized by an inhibition period, due to the slow consumption of the

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

mediating agent and hence slow formation of surface active z-mers (oligo­ mers with chain length that gives sufficient hydrophobicity). 4.3.3 Characteristics of the Individual CRP Techniques in Miniemulsion Polymerization A large number of monomers have been used for RAFT-mediated poly­mer­ i­za­tion in miniemulsion, such as styrene (S), methyl methacrylate (MMA), (2-ethyl)hexyl methacrylate (EHMA), methacrylic acid (MAA), n-butyl acrylate (n-BA), etc. Chain extension of the resulting homopolymers to form block copolymers (via seeded emulsion poly­mer­i­za­tion) has been carried out [40,41,56]. Anionic and cationic low molecular weight surfactants and nonionic polymeric surfactants have been investigated for their influence on the stability of the latex particles. Provided that the concentration of surfactant (stabilization against coalescence/coagulation) and hydrophobe (stabilization against monomer diffusion [Ostwald ripening]) are sufficiently high, stable latex particles with a minimum of coagulation can be synthesized via RAFT-mediated poly­mer­i­za­tion in miniemulsion [57]. Care has to be taken that the pH of the system is properly buffered because RAFT agents are sensitive toward hydrolysis at elevated pH [58,59]. Commonly observed phenomena in RAFT-mediated poly­mer­i­za­tion are an inhibition period and a retardation of the rate of poly­mer­i­za­tion compared to conventional radical poly­mer­i­za­tion [60]. These are disadvantages that particularly limit industrial application. It has been suggested that rate retardation in RAFT-mediated (mini)emulsion poly­mer­i­za­tion could be caused by exit of the leaving group radical into the aqueous phase [61] or by using a block copolymer stabilizer that contains a poly(acrylic acid) (PAA) block [34]. PAA is susceptible to proton abstraction, which results in formation of midchain radicals (MCRs) that propagate slowly and terminate quickly. ATRP in miniemulsion is commonly carried out via “activators generated by electron transfer (AGET) ATRP” [62,63]. Cu(II) is added as the catalyst precursor, which is more stable to oxygen than Cu(I). This circumvents the use of Cu(I) species that is very sensitive to oxidation, which would occur during the formation of a miniemulsion via sonication. AGET ATRP uses a reducing agent such as ascorbic acid, instead of a conventional radical initiator, to create the activator [62,63]. A substoichiometric ratio of reducing agent is used to leave some excess of Cu(II) species to regulate ATRP. This approach also increases the tolerance of the system to air, as the reducing agent can be used to scavenge oxygen from the air. The presence of air would, however, require an increased amount of reducing agent. The optimal amount of the reducing agent depends on the partitioning of the Cu(II) species between the aqueous phase and the monomer droplets, ATRP equilibrium constant, target molecular weight, etc. Too small an amount of reducing agent would lead to very slow poly­mer­i­za­tion, whereas too high an amount of reducing agent would deteriorate the control over the poly­mer­i­za­tion. Partitioning of

Block, Graft, Star, and Gradient Copolymer Particles

109

the more hydrophilic Cu(II) species between the oil and aqueous phases disturbs the Cu(I)-to-Cu(II) ratio, which is undesirable as this ratio regulates the control over the poly­mer­i­za­tion. Another advantage of AGET ATRP is the ability to synthesize pure block copolymers without the formation of homopolymer, as no free radicals are present that initiate new chains during the formation of the second block. The earlier developments of reverse ATRP and simultaneous reverse and normal initiation (SR&NI) ATRP also allowed for application in miniemulsion. However, reverse ATRP employs an external initiator (such as AIBN) to reduce the Cu(II) to Cu(I) and therefore this technique does not allow for the formation of block copolymers. SR&NI ATRP employs a normal alkyl halide initiator in combination with a conventional radical initiator and thus allows for the synthesis of block copolymers and structures of more complex architecture. In addition, a significantly decreased concentration of catalyst is required. However, as a conventional radical initiator is used for the generation of radicals, the synthesis of a block copolymer also leads to the formation of homopolymer impurity from poly­mer­i­za­tion of the second monomer, which requires an additional purification step. Initial attempts to adopt “normal” ATRP in miniemulsion provided moderate success [64,65]. Only if a stable initial emulsion was obtained did the poly­mer­i­za­tion proceed in a controlled manner, that is, linear increase of molecular weight with conversion and low PDI throughout the reaction. An inherent disadvantage to ATRP is the use of a transition metal catalyst (mostly copper), which may be undesirable as it is retained as an impurity after the poly­mer­i­za­tion. The development of “activators re-generated by electron transfer (ARGET) ATRP” [68], which is similar in concept to AGET ATRP, allowed for the use of only parts per million (ppm) amounts of copper catalyst in the poly­mer­i­za­tion medium, while control over the poly­mer­i­za­ tion was retained [66–68]. This development is a big step forward to application in industrial processes. Interaction of anionic surfactants with the copper catalyst results in poor control over molecular weight and molecular weight distribution. Nonionic surfactants can be used in ATRP instead, but they are generally not as preferable as they give bigger particle sizes, result in less stable latexes, and become less effective at elevated temperatures [37]. The development of the “second-generation” nitroxides in NMP provided a solution to the high temperatures required for activation of the TEMPOderived alkoxyamine (Scheme 4.3) [69–71]. The equilibrium constant of these second-generation nitroxides is much higher at lower temperatures and therefore an acceptable rate of poly­mer­i­za­tion is obtained. In addition, the second-generation nitroxides allow for controlled poly­mer­i­za­tion of (meth)­ acrylates. An example is the commercially available nitroxide SG1 (DEPN, Scheme 4.3), which can be used at temperatures of 90–120°C. Due to the formation of a large amount of dead chains at high conversion during the synthesis of homopolymer via NMP in miniemulsion, it is important to keep the conversion low to render the majority of chains active for

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the synthesis of block copolymers. Alternatively, nitroxide end-capped oligo­ mers can be synthesized in bulk or solution and applied as both hydrophobe and mediating agent to miniemulsion poly­mer­i­za­tion [69]. 4.3.4 Nanoparticles with Complex Architecture Synthesized via CRP in (Mini)emulsion The successful application of CRP in heterogeneous media allows for the synthesis of nanoparticles with complex architectures such as block [40,41,44–51,53,54], graft [10,20], star, and gradient [72] copolymers in (mini)emulsion. The synthesis of these structures does not cause additional complexity to the system compared to the synthesis of homopolymers in (mini)emulsion. RAFT-mediated polymerization H Z S S H Z

S

H Miniemulsion polymerization of n-BA

H S

T = 75°C, AIBN, Brij 98, hexadecane

Z

H

Z

S

S

H PBA

H

S

S H

PBA

Z=CH3CH2CH2CH2S H

Z

Z

S

S

H PBA

H

PS

S PS

PBA

Sty, AIBN

S

T = 75°C

H

ATRP H2C

CuBr, PMDETA, EBiB

O O

T = 50°C, bulk

CH3

Br PMA

CuBr2, BPMODA, Sty, Brij 98, hexadecane, ascorbic acid

Br

T = 80°C, miniemulsion

PMA

PS

NMP H2C

O O

T = 115°C 2.5 mol% free SG1

C4H9 +

O N

O

N

O P

OCH3

Conversion to ~80%

O H3CO

PBA O

OC2H5

OC2H5 T = 115°C

O P

H2C

OC2H5

OC2H5 CH3-O(CO)-CH(CH3)-SG1

PBA

PS O

O OCH3

Scheme 4.6 Block copolymer synthesis via CRP in miniemulsion.

N

O P

OC2H5

OC2H5

111

Block, Graft, Star, and Gradient Copolymer Particles

(a)

(b)

250 nm

250 nm (c)

(d)

250 nm (e)

250 nm (f )

500 nm

500 nm

Figure 4.1 Height (a, c, and e) and phase (b, d, and f) images obtained with AFM from poly­mer brushes synthesized via AGET ATRP in miniemulsion, using various ratios of ascorbic acid to Cu(II): 0.20 (a and b) and 0.35 (c–f). Monomer conversion is ~21% for images a and b, ~25% for images c and d, and ~80% for images e and f. (Reprinted from K. Min, S. Yu, H.-I. Lee, L. Mueller, S. S. Sheiko, and K. Matyjaszewski, Macromolecules 40: 6557–63, 2007. With permission.)

Figures 4.1 and 4.2 show examples of atomic force microscopy (AFM) and transmission electron microscopy (TEM) images of polymers with complex architecture obtained in mini(emulsion). Min et al. synthesized poly­mer brushes by growing PBA chains from a poly­mer backbone via AGET ATRP directly in miniemulsion [10]. Figure 4.1 shows the corresponding height and phase images obtained with AFM from these poly­mer brushes for various ratios of ascorbic acid to Cu(II) used, at a given conversion for n-BA. Dire et al. reported on the surfactant-free ab initio batch emulsion poly­mer­ i­za­tion of MMA using a P(MMA-co-S)-SG1 macroalkoxyamine that simultaneously acted as initiator and stabilizing agent [49]. The TEM images they

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

500 nm Figure 4.2 TEM images obtained from surfactant-free ab initio batch emulsion poly­mer­i­za­t ion of MMA using a P(MMA-co-S)-SG1 macroalkoxyamine initiator. (Reprinted from C. Dire, S. Magnet, L. Couvreur, and B. Charleux, Macromolecules 42: 95–103, 2009. With permission.)

obtained from their stable latexes show a very narrow particle size distribution, as can be seen in Figure 4.2. Provided that stable latex particles are obtained, employment of the appropriate mediating agent during the poly­mer­i­za­tion (e.g., Scheme 4.7) will result in the formation of graft or star copolymers. The synthetic route is similar to that in homogeneous media, with the additional benefit in heterogeneous media of less termination/coupling reactions. Although coupling reactions can still occur within the latex particles, macroscopic gel formation will not occur as long as the (mini)emulsion system remains stable [10]. Cross-linking will not affect the fluidity of the system and therefore high conversions can be achieved. Although the synthetic route is not significantly more complex compared to the synthesis of block copolymers, few reports have appeared on the synthesis of graft and star copolymer nanoparticles directly in (mini)emulsion. H2C

O O

1. BPMODA, Cu(II)Br2, EBiB, hexadecane, T = 80°C Aqueous solution of Brij 98 2. AscA, t-BA (0.01 mL/min for 200 min) gradient n-BA - t-BA copolymer

H3C

Scheme 4.7 AGET ATRP of n-BA with a constant feed of tert-butyl acrylate (t-BA) in miniemulsion for the synthesis of gradient copolymers with controlled molecular weight and low polydispersity. (Reprinted from K. Min, J. K. Oh, and K. Matyjaszewski, Journal of Polymer Science, Part A: Polymer Chemistry 45: 1413–23, 2007. With permission.)

The synthesis of gradient copolymers has been reported for ATRP, where AGET ATRP was used for the synthesis of forced gradient copolymers [72]. The absence of a conventional radical initiator for the reduction of the precursor catalyst Cu(II) provides that the polymers exclusively be initiated via the

Block, Graft, Star, and Gradient Copolymer Particles

113

ATRP initiator, and therefore does not result in the formation of homopolymer. Factors that influence the gradient are, for example, the molar feed ratio of the monomers, the feeding rate, the hydrophobicity of the monomers, and the reactivity ratios of the monomers. SR&NI ATRP is not suitable for the forced gradient method because M2 is fed to the reaction mixture. Radicals derived from a conventional radical source could escape monomer droplets where the poly­mer­i­za­tion takes place, and initiate poly­mer­i­za­tion of M2 in the aqueous phase to form homopolymer of M2. This not only broadens the molecular weight distribution, but also leads to the formation of unstable latexes.

4.4 Polymer Nanoparticles via Self-Assembly 4.4.1 Synthesis of Amphiphilic Copolymers Most poly­mer­i­za­tion techniques can be used to synthesize amphiphilic copolymers. Several poly­mer­i­za­tion techniques can be used in tandem for the synthesis of amphiphilic copolymers with complex architectures. This requires that several functional groups or initiating/mediating agents are present either at the chain end (block copolymer synthesis) or along the poly­ mer backbone (for grafting reactions) or at the junction (for star copolymer synthesis). The amphiphilic nature is a result of having different poly­mer blocks in the same molecule that have different properties. Synthesis of complex macromolecular architectures by CRP has been highlighted already in the previous section. A combination of ATRP and “click chemistry” is widely used for the synthesis of amphiphilic copolymers. ATRP and click chemistry were used, for example, to synthesize a multiresponsive double hydrophilic ABC miktoarm star terpolymer [73] and two oppositely charged graft ionomers consisting of poly(methacrylic acid-co-­azidopropyl methacrylate)-g-poly(N-isopropyl acrylamide) (P[MAA-co-AzPMA]-g-P[NIPAM]) and methyl iodide quaternized poly(2-[dimethylamino]ethyl methacrylate-coazidopropyl methacrylate)-g-poly(N-isopropyl acrylamide) (P[DMAEMAco-AzPMA]-g-P[NIPAM]) [74]. ATRP was used to graft tert-butyl acrylate (t-BA) onto polystyrene-b-ethylene-co-butylene-b-polystrene (PSEBS) backbone [75]. The ATRP macroinitiator was initially prepared by hydrogenation and chloro­methylation of PSEBS. Free radical poly­mer­i­za­tion in conjunction with coupling chemistry can also be used to synthesize amphiphilic copolymers. A cross-linkable amphiphilic graft copolymer was synthesized via free radical poly­mer­i­za­tion of N-acryloxysuccinimide (NAS) as the backbone, and then HEMA, amino-functionalized polyethylene glycol (PEG), and amino-functionalized PNIPAM were attached to the backbone [76]. Other techniques such as ROP [77,78] and ROMP [79] can also be used to synthesize amphiphilic copolymers. Anionic poly­mer­i­za­tion was used to synthesize

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

tri­block terpolymers that self-assemble in organic media [80]. A combination of ATRP and anionic poly­mer­i­za­tion was used to synthesize star-like amphiphilic copolymers [81]. 4.4.2 Nanostructures via Self-Assembly of Copolymers Self-assembly of amphiphilic copolymers such as block [82,83], star [84–87], and graft copolymers [74,76,88–90] into nanostructures have been reported by various authors. Amphiphilic copolymers have a tendency of self­assembling into morphologies such as micelles, vesicles, lamellae, etc. when a selective solvent for one of the blocks is added. The driving force for self-assembly is the reduction in surface energy. The commonly used self-­assembly procedure is to synthesize the copolymer (or dissolving the copoly­mer) in its common solvent (solvent for all the blocks) followed by solvent exchange with a selective solvent via dialysis. The self-assembly of these copoly­mers is reversible upon addition of a common solvent for the copolymer and upon heating. It is important to note that the self-assembled copolymers are thermodynamically and kinetically more stable than self-assembly structures from low molecular weight molecules [91]. The process of self-assembly of amphiphilic copolymers is affected by a number of factors, which include their chemistry, topology, molecular weight, (co)solvent, etc. Self-assembly of copolymers is also induced by incorporating thermo- or pH-responsive poly­mer chains in the copolymer, and thus nanostructures are formed upon a variation in the pH or temperature [92–97]. A double hydrophilic ABC mikto­arm star terpolymer made up of PEG, PNIPAM, and poly(2-[diethylamino]ethyl methacrylate) (PDEAEMA) blocks was shown to self-assemble at 25°C and pH 10 and at 50°C and pH 4 but remained in solution at 25°C and pH 4 [73]. Narain and Armes used an aldehyde-­functionalized ATRP initiator to synthesize various sugar containing methacrylate block copolymers (glyco­polymers) that showed either pHor thermo-responsive behavior [98]. These copolymers formed well-defined micelles upon self-assembly, and the ­aldehyde-functional groups were found on the periphery of the micelles. Inverse polymeric micelles comprising a hydrophilic core and a hydrophobic shell can also be prepared. For example, micelles of an AB copolymer in a selective solvent for A can be reversed by adding a selective solvent for B while removing the selective solvent for A via dialysis. Cheng et al. prepared inverse polymeric micelles in chloroform using polystyrene-b-poly(4vinylpyridine) block copolymer by in situ quaternization of the pyridine moiety using HCl, and Figure 4.3 shows the latex particles obtained by varying the transfer time [99]. Self-assembly of macromolecules is useful for commercial applications such as coatings, detergents, cosmetics, electronics, thin films, drug delivery, and biocompatibility. The self-assembly structures are usually studied using (cryo) TEM, light scattering, and small-angle X-ray scattering. Freeze

Block, Graft, Star, and Gradient Copolymer Particles

(a)

(b)

(c)

(d)

(e)

(f)

115

Figure 4.3 TEM images of PS-b-P4VP inverse micelles at different transfer times (t): (a) 3 min, (b) 15 min, (c) 10 h, (d) 24 h, (e) 120 h, and (f) is the TEM image of PMACs (t = 120 h) noncovalently crosslinked by bivalent S2O82– ions. All the scale bars are 200 nm in length. (Reprinted from F. Cheng, X. Yang, H. Peng, D. Chen, and M. Jiang, Macromolecules 40: 8007–14, 2007. With permission.)

drying can be used to remove water without disrupting the micellar structure, allowing techniques such as AFM to be used. 4.4.3 Nanoparticles Synthesis by Cross-Linking of Self-Assembled Structures Synthesis of poly­mer nanoparticles is done via cross-linking of self-assembly structures of block, star, and graft copolymers. The synthesis of cross-linked nanoparticles requires cross-linkable groups to be part of the self-assembled structure. Scheme 4.8 illustrates different domains in the self-assembled structures that can be selectively cross-linked. Cross-linking of self-assembled structures will result in poly­mer nanoparticles that are resistant to changes in solvent, temperature, pH, or ionic strength. The advantage of cross-linking of self-assembly structures over synthesis in heterogeneous media for nanoparticle synthesis is that amphiphilic poly­mer nanoparticles of complex copolymer architectures can be easily

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Copolymer Self assembly

Cross-linking

Shell cross-linking at the hydrophilic end

Cross-linked shell

Cross-linked core

Core cross-linking at the hydrophobic end

Scheme 4.8 Cross-linking of micelles at various possible strategic positions.

synthesized whereas their synthesis in emulsion may be more complex and induce latex stability problems. Depending on the position of the cross-linkable moieties in the copolymer, cross-linking can be carried out in the shell at the hydrophilic chain end, in the shell along the hydrophilic poly­mer backbone, at the hydrophilic­hydrophobic interface of the block copolymer, in the core along the hydrophobic poly­mer backbone, and in the core at the hydrophobic chain end [100]. The cross-linking density and the position of cross-links in the micellar structure hugely affect properties such as permeability, swellability, thermal stability, reactivity, etc. of the poly­mer nanoparticles. It is important to note that the self-assembled structures are preserved after adequate cross-linking at various strategic positions using various chemistries. Most research in this field focused on cross-linked, self-assembled structures of amphiphilic block copolymers. O’Reilly et al. wrote a brief review on block copolymers that self-assemble into poly­mer micelles in a selective solvent and that possess functional groups throughout the core and/or shell for cross-linking purposes [100]. Guo et al. synthesized cross-linked diblock copolymer micelles of polystyrene-b-poly(cinnamoylethyl methacrylate) (PS-b-PCEMA) via photo-cross-linking of the PCEMA block [101]. Figure 4.4 shows TEM images of core photo-cross-linked diblock copolymer micelles illustrating that increasing the molecular weight of both blocks of the diblock copolymer resulted in an increase in the particle size.

117

Block, Graft, Star, and Gradient Copolymer Particles

(a)

(b)

250 nm

100 nm

Figure 4.4 Transmission electron micrographs of core cross-linked diblock copolymer micelles; (a) PS276-bPCEMA90 and (b) PS302-b-PCEMA570. (Reprinted from A. Guo, G. Liu, and J. Tao, Macromolecules 29: 2487–93, 1996. With permission.)

A number of cross-linking chemistries can be employed for cross-linking of self-assembled structures. End-functionalized amphiphilic copolymers are required for shell and core cross-linking at hydrophilic or hydrophobic poly­mer chain end, respectively. Scheme 4.9a shows examples of functional groups that can be used for cross-linking of copolymers at the chain end. Self-assembly of end-functionalized copolymers presents the functional groups at either the exterior or interior of the self-assembled structures. The (a) Examples of functional groups for cross-linking or modification 1

alkynyl

N3 azide

5

(b) Examples of vinyl cross-linkers 9

O 2 H aldehyde 3

O acrylate 4

OH alcohol

N3 12 N3 1,4-diazidobutene

1,4-divinylbenzene 6 H2N amine 7 O

O

(c) Examples of chemical cross-linkers

O

13 O

NH

O O N,N’-methylenebisacrylamide

ketone 8

NH 10

OH

carboxylic acid

CH3 11

O

O O

O CH3

ethylene glycol dimethacrylate

glutaraldehyde

NH2 14 H2N ethylenediamine 15

O dipropagyl ether

(d) Examples of (co)monomers that impart functional groups for cross-linking or modification CH3 CH3 N O N H3C O O O O 19 O 16 O 17 O 18 2-vinylpyridine (2-VP) 21 N O O O OH N-acryloxysuccinimide (NAS) 20 OH N3 2-hydroxy ethyl methacrylate acrylic acid (AA) (HEMA) 3-azidopropyl methacrylate (AzPMA)

O

CH

O

CH3 O

7-(2-methacryloxyethoxy)4-methylcoumarin

Scheme 4.9 Examples of (a) end-functional groups, (b) vinyl cross-linkers, (c) chemical cross-linkers, and (d) vinyl (co)monomers that can be used for cross-linking and modifying cross-linked nanoparticles.

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

end-functional groups may also include RAFT moieties, ATRP initiators, and vinyl groups (i.e., macromonomer) that allow poly­mer chains to be crosslinked using a difunctional vinyl monomer (Scheme 4.9b). The copolymer chain end can also be functionalized with functional molecules and then cross-linked after self-assembly using multifunctional complementary molecules. Scheme 4.9c shows examples of chemical cross-linkers. Graft copolymers (a) P(AA-co-MEA)-g-PNIPAM and (b) P(AA-co-MEA)-g(PNIPAM and PEG) were synthesized by grafting amine-terminated polymers PNIPAM and PEG onto P(NAS-co-MEA) backbone [76]. The unreacted NAS units in the copolymer backbone were then hydrolyzed forming acrylic acid residues. Cross-linking of the MEA residues after thermally induced self-assembly of the graft copolymer was performed using ammonium persulfate, and Figure  4.5 shows the TEM images of the graft copolymers (a) P(AA-co-MEA)-g-PNIPAM and (b) P(AA-co-MEA)-g-(PNIPAM and PEG). Graft copolymer (a) resulted in bulk cross-linking while graft copolymer (b) resulted in exclusively shell cross-linking. Cross-linking of the shell or the core is done through cross-linkable groups in the shell or core of the self-assembled structures. Some functional monomers (Scheme 4.9d) can be used in copoly­mer­i­za­tion or in modification of the copolymer to provide cross-linkable groups. Bütün et al. reported on the synthesis of shell cross-linked block copolymer micelles with tunable hydrophilic/hydrophobic cores [102]. The core consisted of a thermo-responsive poly(N-[morpholino]ethyl methacrylate) (PMEMA) block that is hydrophilic at room temperature and hydrophobic above its lower critical solution temperature (LCST). Cross-linking of the PDMAEMA shell

(a)

(b)

100 nm

100 nm

Figure 4.5 TEM images of cross-linked micelles (a) P(AA-co-MEA)-g-PNIPAM and (b) P(AA-co-MEA)-g(PNIPAM and PEG). (Reprinted from W.-H. Chiang, Y.-H. Hsu, T.-W. Lou, C.-H. Chern and H.-C. Chiu, Macromolecules 42: 3611–19, 2009. With permission.)

119

Block, Graft, Star, and Gradient Copolymer Particles

above the LCST of PMEMA resulted in preserved micellar structure upon cooling to room temperature. Copolymers with carboxylic acid or amine functional groups in the hydrophilic part allow cross-linking to be done in the shell (or the core for inverse micelles). Scheme 4.9c shows examples of chemical cross-linkers. Difunctional amines such as 2,2’-(ethylenedioxy)bis(ethylamine) and aldehydes such as glutaraldehyde are used to cross-link the carboxylic acid and amino functional groups, respectively. Multifunctional (>2) molecules are statistically better cross-linkers. Monomers such as 2-vinyl pyridine (2VP) and NAS can be used in the copolymer and then cross-linked using difunctional halogenated molecules such as 1,4-dibromobutane and difunctional alcohols, respectively. Azide functionalized methacrylate can be used in copoly­mer­i­ za­tion to allow for cross-linking reactions with difunctional alkynyls such as dipropargyl ether. Monomers such as 2-hydroxyethyl methacrylate (HEMA) can be used to react with PNAS units in a copolymer to allow for free radical cross-linking. It is also possible to cross-link micelles at the hydrophilic-hydrophobic interface. Scheme 4.10 shows how ATRP and click chemistry can be used to specifically functionalize a copolymer at the hydrophilic-hydrophobic interface. Self-assembly of the amphiphilic copolymer will result in the monomer functionality at the hydrophilic-hydrophobic interface. Cross-linking of the micelles is then done using a difunctional or multifunctional free radical monomer. Alternatively the hydrophilic-hydrophobic interface can be modified with chemical groups, and the micelles are then stabilized by cross-linking using multifunctional cross-linkers. O

O

OH

Br O

O

O

(eg PEG-OH) OH O

Br O

CH

O O

N N

CH

CH

OH

N

N3

HC

DCC DMAP CH2Cl2 HO O

O

H3C

OH

Br

ATRP monomer (eg. MMA)

O O O

O

O CH3 O ‘click chemistry’

O O

O

O 1) self-assemble 2) cross-linking CH3 O O O CH3 EGDMA O

cross-linking at the hydrophilic-hydrophobic interface of micelles

Scheme 4.10 An example of cross-linking chemistry at the hydrophilic-hydrophobic interface.

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Advanced Polymer Nanoparticles: Synthesis and Surface Modifications

Another method that can be used to cross-link micelles at the hydrophobic-hydrophilic interface is to use an ABC amphiphilic miktoarm star copolymer, for example. One of the blocks will be hydrophobic and the other two hydrophilic. One of the hydrophilic blocks should be pH- or thermoresponsive and bear cross-linkable groups. The micellization is carried out at normal conditions; then pH or temperature is changed and this results in the collapse of the pH- or thermo-responsive block. Cross-linking of this block is then carried out under these conditions to form micelles cross-linked at hydrophobic-­hydrophilic interface, and a change in the pH or temperature will have little or no effect on the cross-linked block. Alternatively, an ABC triblock copolymer can be synthesized with crosslinkable B-block, which can be varied in length and solubility in selective solvents for both A and C. The A and C blocks are designed to be hydrophilic and hydrophobic, respectively. Self-assembly of the triblock copolymer will position block B at the hydrophilic-hydrophobic interface and cross-linking of B can be carried out. Liu et al. synthesized a thermo-responsive triblock copoly­mer that formed micelles, and cross-linking of the micelles was performed on the central block to avoid intermicellar cross-linking [103]. Intermicellar cross-linking during shell cross-linking is also avoided or minimized using dilute conditions. Figure 4.6 shows a TEM image of a PEO-b-PDMAEMA-b-PMEMA (PMEMA = poly[N-morpholino]ethyl methacrylate) micelles cross-linked at the PDMAEMA block [104].

250 nm Figure 4.6 Transmission electron micrograph of a dilute suspension of cross-linked micelles prepared using the PEO-PDMAEMA-PMEMA triblock copolymer. (Reprinted from V. Bütün, X.-S. Wang, M. V. d. P. Banez, K. L. Robinson, N. C. Bilingham, and S. P. Armes, Macromolecules 33: 1–3, 2000. With permission.)

Block, Graft, Star, and Gradient Copolymer Particles

121

4.4.4 Functionalization of Cross-Linked Micelles Nanoparticles can be designed to have a particular functionality on the surface or in its interior to allow further modification. Amphiphilic copolymers have long poly­mer chain segments in both the hydrophilic and hydrophobic parts in which specific functional groups can be incorporated. After selfassembly and cross-linking, some of the functional groups may reside on the surface (for functional groups in the hydrophilic part) or interior (if functional groups are in the hydrophobic part) of the nanoparticles. The residual functionality is then used for modification of the poly­mer nanoparticles with (bio)macromolecules or fluorescent labels, for example. The use of functional initiators and CRP mediators (ATRP initiator, RAFT agent, alkoxyamine [NMP]) will result in cross-linked micelles with functional groups on the surface or in the micellar interior, which can be utilized for further CRP. Scheme 4.11 shows chemistries that have been used to modify the surface of cross-linked copolymer micelles. Alternatively, the copolymers can be functionalized first with organic, (bio)molecules, dyes, etc., followed by self-assembly and then cross-linking. A biotin-functionalized ATRP-initiator was used to synthesize a poly(acrylic acid)-b-poly(methyl acrylate) (PAA-b-PMA) block copolymer [105]. After selfassembly of the block copolymer and cross-linking of the shell, the biotin functionality was retained at the surface of the nanoparticles. 4.4.5 Potential Applications of Cross-Linked Nanoparticles Polymeric micelles have great potential application in the drug delivery field as nanocarriers. These self-assembled micelles have been widely studied in the field of drug delivery because hydrophobic drugs can be retained within the hydrophobic inner core of micelles. Chan et al. synthesized reversible core cross-linked micelles of an amphiphilic block copolymer for drug release studies [106]. The drug loading in the core cross-linked micelles was high (60 wt%) and the hydrolysis of the cross-links due to acidic pH resulted in faster drug release at low pH than at neutral pH. Liu et al. investigated the potential use of double hydrophilic block copolymers as carrier [83]. An aldehyde-modified ATRP initiator was used to prepare a triblock copolymer consisting of poly(oligo[ethylene glycol]methyl ether methacrylate((POEGMA), PDMAEMA, and PDEAEMA blocks (POEGMA-b-PDMAEMA-b-PDEAEMA) that self-assembled into micelles at alkaline pH and that molecularly dissolved at acidic pH. The middle block was cross-linked at alkaline pH to obtain shell cross-linked micelles that showed reversible pH-responsive ­swelling/deswelling behavior and formed bioconjugates by covalently attaching lysozyme to the aldehyde functionality of the triblock copoly­mer. Stenzel wrote a feature article showing how RAFT can be used to synthesize micelle-forming block copolymers for drug encapsulation and release [107].

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NH2

H2N

NH2

H2N

NH2

H2N

CH3-O

OH H N—R 2

O

O O

H

O

NH

NH

O NH2

Other coupling functional groups O H aldehyde

O

O H3C ketone

HO carboxylic acid

O

R—NH

NH—R O

O R

R = polymer chain, peptide, protein, dye etc. R= R=

N3 Further functionalization via ‘click chemistry’

O

HN

N

H

H

O

O H

NH2 NH

R

OH

O

HN

O

HO

NH

H N O 2

H2N O

NH2

NH2

HO

O

H2N—

H

N

O

O

Other coupling functional groups HO

BrMg

N

Br

Br

Br

Br

CRP grafting Br

Br

Br

Br

Br Br

Br

N3

Br 1) NaN3

2)

Br

Br

N N

N

N

Br

N N

N3

: polymer chain, protein, enzyme, dye, drug etc.

Scheme 4.11 Examples of surface modification reactions for cross-linked poly­mer nanoparticles.

Inorganic reactions can also be carried out in so-called poly­mer micelles with aqueous core (PMACs). Inorganic compounds such as silica, AgCl, and Fe(SCN)2+ were synthesized in the aqueous core of a polystyrene-b-poly(4vinylpyridine) (PS-b-P4VP) micellar structure [99]. Shell cross-linked micelles of poly([ethylene oxide]-b-glycerol monomethacrylate-b-[diethylamino]ethyl methacrylate) (PEO-b-PGlMA-b-PDEAEMA) were used as pH-responsive particulate emulsifers [108].

Block, Graft, Star, and Gradient Copolymer Particles

123

Reversible cross-linking has been employed in cross-linking of micelles. Controlled release of bioactive agents can be achieved by regulating the reversibility of the cross-linked micelles. Reversible cross-linking of micelles provides stability to the micelles due to cross-links and facilitates faster release of the contents (drugs, polymers, or inorganic products) due to cleavage of the cross-links. Several authors used disulfide links as degradable cross-links [80,109–111]. For example, Li et al. synthesized an ABC triblock copolymer that was thermo-responsive and underwent reversible cross-linking [111]. The triblock copolymer PEO-b-P(DMAEMA-stat-NAS)b-PNIPAM was cross-linked through the NAS units using cystamine. The cross-linked micelles were reductively cleaved using dithiothreitol or tris(2-carboxyethyl)phosphine and re-cross-linked by adding cystamine. Molecules that dimerize and decouple due to changes in external stimuli can also be used as reversible cross-links. Babin et al. synthesized a PDMAEMA-b-P(MMA-co-coumarin methacrylate [CMA]) (PDMAEMA54b-P[MMA55 -co-CMA19]) copolymer using ATRP and prepared reversible shell cross-linked poly­mer micelles that were stimuli responsive [110]. Thus, poly­mer chains in the copolymer were modified with coumarin molecules which cross-link at UV > 310 nm and de-cross-link at UV < 260 nm.

4.5 Conclusions Nanoparticles of block, graft, star, and gradient copolymers can be synthesized in dispersed systems and via cross-linking of self-assembled copolymers. The two routes to copolymer nanoparticles can be fine-tuned to produce particles of the required size and properties (both chemical and physical). The method for synthesis of copolymer nanoparticles depends entirely on the intended application. Polymerization in dispersed systems can be carried out in either oil-in-water or water-in-oil (inverse dispersion), and large-scale synthesis of copolymer nanoparticles is possible. CRP has been successfully applied to poly­mer­i­za­tion in dispersed systems to synthesize well-defined copolymer topologies. There is, however, limited literature on the synthesis of complex copolymer architectures such as star and graft copolymers in dispersed systems, although the synthetic tools are at hand. Copolymer nanoparticles synthesized via poly­mer­i­za­tion in dispersed systems are widely used in industry for various applications. The self-assembly route of making copolymer nanoparticles is relatively simple since the copolymer can be synthesized in any suitable media. Generally, all poly­mer­i­za­tion techniques can be employed for the synthesis of copolymers that have the ability to self-assemble. The copolymer can be purified

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before self-assembly and cross-linking. This route, however, applies only to copoly­mer architectures that are capable of self-assembly. Copolymer nanoparticle modification is easier on self-assembled nanoparticles, and both surface (shell) and core functionalization can be carried out selectively. Applications of cross-linked self-assembled copolymers are very broad and are not limited to the drug delivery and stimuli- (pH, temperature, ionic strength) responsive fields.

References



















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