Temperature-Responsive Polymers: Chemistry, Properties, and Applications

An authoritative resource that offers an understanding of the chemistry, properties and applications of temperature-responsive polymers With contributions from a distinguished panel of experts, Temperature-Responsive Polymers puts the focus on hydrophilic polymers capable of changing their physicochemical properties in response to changes in environmental temperature. The contributors review the chemistry of these systems, and discuss a variety of synthetic approaches for preparation of temperature-responsive polymers, physicochemical methods of their characterisation and potential applications in biomedical areas. The text reviews a wide-variety of topics including: The characterisation of temperature-responsive polymers; Infrared and Raman spectroscopy; Applications of temperature-responsive polymers grafted onto solid core nanoparticles; and much more. The contributors also explore how temperature-responsive polymers can be used in the biomedical field for applications such as tissue engineering. This important resource: Offers an important synthesis of the current research on temperature-responsive polymers Covers the chemistry, the synthetic approaches for presentation and the physiochemical method of temperature-responsive polymers Includes a review of the fundamental characteristics of temperature-responsive polymers Explores many of the potential applications in biomedical science, including drug delivery and gene therapy Written for polymer scientists in both academia and industry as well as postgraduate students working in the area of stimuli-responsive materials, this vital text offers an exploration of the chemistry, properties and current applications of temperature-responsive polymers.

Table of Contents:
About the Editors xiii List of Contributors xv Preface xix Part I Chemistry 1 1 Poly(N-isopropylacrylamide): Physicochemical Properties and Biomedical Applications 3 Marzieh Najafi, Erik Hebels,WimE. Hennink, and Tina Vermonden 1.1 Introduction 3 1.2 PNIPAM as Thermosensitive Polymer 4 1.3 Physical Properties of PNIPAM 5 1.3.1 Phase Behavior of PNIPAM in Water/Alcohol Mixtures 5 1.3.2 Effect of Concentration and Molecular Weight of PNIPAM on LCST 5 1.3.3 Effect of Surfactants on LCST 7 1.3.4 Effect of Salts on LCST 7 1.4 Common Methods for Polymerization of NIPAM 8 1.4.1 Free Radical Polymerization 8 1.4.2 Living Radical Polymerization 9 1.4.2.1 ATRP of NIPAM 10 1.4.2.2 RAFT Polymerization of NIPAM 11 1.5 Dual Sensitive Systems 12 1.5.1 pH and Thermosensitive Systems 12 1.5.2 Reduction-Sensitive and Thermosensitive Systems 13 1.5.3 Hybrid-Thermosensitive Materials 13 1.6 Bioconjugation of PNIPAM 15 1.6.1 Protein–PNIPAM Conjugates 16 1.6.2 Peptide–PNIPAM Conjugates 18 1.6.3 Nucleic Acid–PNIPAM Conjugates 21 1.7 Liposome Surface Modification with PNIPAM 21 1.8 Applications of PNIPAM in Cell Culture 22 1.9 Crosslinking Methods for Polymers 23 1.9.1 Crosslinking in PNIPAM-Based Hydrogels 23 1.9.2 Crosslinking of PNIPAM-Based Micelles 26 1.9.2.1 Shell Crosslinked (SCL) 26 1.9.2.2 Core Crosslinked (CCL) 27 1.10 Conclusion and Outlook of Applications of PNIPAM 27 Acknowledgments 28 References 28 2 Thermoresponsive Multiblock Copolymers: Chemistry, Properties and Applications 35 Anna P. Constantinou and Theoni K. Georgiou 2.1 Introduction 35 2.2 Chemistry of Thermoresponsive Block-based Copolymers 35 2.3 Architecture, Number of Blocks and Block Sequence 38 2.3.1 Why the Block Structure? 38 2.3.2 Triblock Copolymers 39 2.3.2.1 Micelles 40 2.3.2.2 Gels 45 2.3.2.3 Films and Membranes 52 2.3.3 Tetrablock Copolymers 53 2.3.4 Pentablock Copolymers 54 2.3.4.1 Pluronic®Based 54 2.3.4.2 Non-pluronic Based 56 2.3.5 Multiblock Copolymers 57 2.4 Applications 59 2.5 Conclusions 61 Acknowledgments 61 References 61 3 Star-shaped Poly(2-alkyl-2-oxazolines): Synthesis and Properties 67 Andrey V. Tenkovtsev, Alina I. Amirova, and Alexander P. Filippov 3.1 Introduction 67 3.2 Synthesis of Star-shaped Poly(2-alkyl-2-oxazolines) 68 3.3 Properties of Star-shaped Poly(2-alkyl-2-oxazolines) 78 3.4 Conclusions 87 References 88 4 Poly(N-vinylcaprolactam): FromPolymer Synthesis to Smart Self-assemblies 93 Fei Liu, Veronika Kozlovskaya, and Eugenia Kharlampieva 4.1 Introduction 93 4.2 Synthesis of PVCL Homo- and Copolymers 93 4.2.1 Synthesis of Statistical PVCL Copolymers 95 4.2.2 Synthesis of PVCL Block Copolymers 97 4.2.3 Other PVCL-based Copolymers 99 4.3 Properties of PVCL in Aqueous Solutions 99 4.3.1 Dependence of the LCST of PVCL on Molecular Weight and Polymer Concentration 99 4.3.2 LCST Dependence on Chemical Composition 100 4.3.3 The Effect of Salt on the PVCL Temperature Response 102 4.3.4 The Effect of Solvent on PVCL Temperature Response 102 4.4 Assembly of PVCL-based Polymers in Solution 102 4.4.1 PVCL Interpolymer Complexes 102 4.4.2 PVCL-based Micelles 103 4.4.3 Self-assembly of PVCL-based Copolymers into Polymersomes 105 4.5 Templated Assemblies of PVCL Polymers 107 4.5.1 Hydrogen-bonded PVCL-based Multilayers 107 4.5.1.1 pH-sensitive Hydrogen-bonded PVCL Multilayers 107 4.5.1.2 Enzymatically Sensitive Hydrogen-bonded PVCL Multilayers 108 4.5.2 Multilayer Hydrogels of PVCL 110 4.6 Outlook and Perspectives 113 Acknowledgment 113 References 114 5 Sodium Alginate Grafted with Poly(N-isopropylacrylamide) 121 Catalina N. Cheaburu-Yilmaz, Cornelia Vasile, Oana-Nicoleta Ciocoiu, and Georgios Staikos 5.1 Alginic Acid 121 5.1.1 Monomeric and Polymeric Structure of Alginates 121 5.2 Poly(N-Isopropylacrylamide) and Thermoresponsive Properties 122 5.3 Synthesis and Characterization of Alginate-graft-PNIPAM Copolymers 123 5.4 Solution Properties 124 5.4.1 Turbidimetry 124 5.4.2 Fluorescence 124 5.4.3 Rheology 126 5.4.4 Degradability 130 5.4.5 Biocompatibility 131 5.4.5.1 Cytotoxicity 132 5.4.5.2 Pharmaceutical and Medical Applications 135 5.5 Conclusions and Perspectives 137 References 138 6 Multi-stimuli-responsive Polymers Based on Calix[4]arenes and Dibenzo-18-crown-6-ethers 145 SzymonWiktorowicz, Heikki Tenhu, and Vladimir Aseyev 6.1 Introduction 145 6.2 Single-stimuli-responsive Polymers 146 6.2.1 Thermo-responsive Polymers in Polar Media 147 6.2.2 pH-responsive Polymers 148 6.2.3 Photoresponsive Polymers 148 6.2.4 Other Single-stimuli-responsive Polymers 150 6.3 Multi-stimuli-responsive Polymers 150 6.4 Poly(azocalix[4]arene)s and Poly(azodibenzo-18-crown-6-ether)s 151 6.4.1 Calixarenes 151 6.4.2 Crown Ethers 152 6.4.3 Structural Units of Poly(azocalix[4]arene)s 153 6.4.4 Structural Units of Poly(azodibenzo-18-crown-6-ether)s 154 6.5 Photoisomerization 154 6.6 Host–guest Interactions 156 6.7 Thermo-responsiveness 158 6.7.1 LCST: Tegylated Poly(azocalix[4]arene)s inWater 158 6.7.2 UCST: Tegylated Poly(azocalix[4]arene)s in Alcohols 159 6.7.3 UCST and Photoisomerization of Tegylated Poly(azocalix[4]arene)s 160 6.7.4 UCST and Poly(azodibenzo-18-crown-6-ether)s 161 6.7.5 UCST and Photoisomerization of Poly(azodibenzo-18-crown-6-ether)s 162 6.7.6 UCST in Water–alcohol Mixtures 162 6.8 Solvatochromism and pH Sensitivity 163 6.9 Summary and Outlook 164 Acknowledgments 165 References 165 Part II Characterization of Temperature-responsive Polymers 175 7 Small-Angle X-ray and Neutron Scattering of Temperature-Responsive Polymers in Solutions 177 Sergey K. Filippov, Martin Hruby, and Petr Stepanek 7.1 Introduction 177 7.2 Temperature-responsive Homopolymers 179 7.3 Hydrophobically Modified Polymers 182 7.4 Cross-Linked Temperature-Sensitive Polymers and Gels 184 7.5 Temperature-Responsive Block Copolymers 185 7.6 Hybrid Nanoparticles 187 7.7 Gradient Temperature-Responsive Polymers 188 7.8 Multi-responsive Copolymers 189 7.9 Concluding Remarks 191 Acknowledgments 191 References 191 8 Infrared and Raman Spectroscopy of Temperature-Responsive Polymers 197 Yasushi Maeda 8.1 Introduction 197 8.2 Experimental Methods to Measure IR and Raman Spectra of Aqueous Solutions 198 8.3 Poly(N-substituted acrylamide)s 200 8.3.1 Overall Spectral Change 200 8.3.2 Amide Bands 202 8.3.3 C–H Stretching Bands 204 8.3.4 C–D Stretching Band 206 8.4 Poly(vinyl ether)s 207 8.5 Poly(meth)acrylates 208 8.6 Effects of Additives on Phase Behavior 210 8.7 Temperature-Responsive Copolymers and Gels 217 References 222 9 Application of NMR Spectroscopy to Study Thermoresponsive Polymers 225 Jiří Spěváček 9.1 Introduction 225 9.2 Coil–Globule Phase Transition and Its Manifestation in NMR Spectra 225 9.3 Temperature Dependences of High-Resolution NMR Spectra: Phase-Separated Fraction p 227 9.4 Multicomponent Polymer Systems 230 9.5 Effects of Low-Molecular-Weight Additives on Phase Transition 234 9.6 Behavior of Water at the Phase Transition 236 9.7 Conclusion 242 Acknowledgment 242 References 242 10 Polarized Luminescence Studies of Nanosecond Dynamics of Thermosensitive Polymers in Aqueous Solutions 249 Vladimir D. Pautov, Tatiana N. Nekrasova, Tatiana D. Anan’eva, and Ruslan Y. Smyslov 10.1 Introduction 249 10.2 Theoretical Part 250 10.2.1 Polarization of Luminescence 250 10.2.2 The Use of Polarized Luminescence in the Studies of Nanosecond Dynamics of Macromolecules 253 10.3 Experimental Part 258 10.3.1 Methods of Synthesis of Polymers Containing Luminescent Markers 258 10.3.2 Technique for Measurement of Luminescence Polarization 260 10.3.3 Thermosensitive Water-Soluble Polymers 263 10.3.4 pH and Thermosensitive Water-Soluble Polymers 268 10.3.5 Temperature-Induced Transitions in Polymers in Nonaqueous Solutions 271 10.4 Conclusion 272 References 273 Part III Applications of Temperature-responsive Polymers 279 11 Applications of Temperature-Responsive Polymers Grafted onto Solid Core Nanoparticles 281 Edward D. H. Mansfield, Adrian C.Williams, and Vitaliy V. Khutoryanskiy 11.1 Introduction 281 11.2 Silica Nanoparticles 282 11.2.1 pNIPAM-functionalised Silica Nanoparticles 282 11.2.2 Poloxamer-functionalised Silica Nanoparticles 284 11.2.3 Other Polymers 286 11.3 Metallic Nanoparticles 286 11.3.1 pNIPAM-functionalised Metallic Nanoparticles 287 11.3.2 Poloxamer-functionalised Metallic Nanoparticles 288 11.3.3 Elastin-functionalised Metallic Nanoparticles 288 11.3.4 Other Polymer-functionalised Metallic Nanoparticles 289 11.4 Magnetic Nanoparticles 290 11.4.1 pNIPAM-functionalised Magnetic Nanoparticles 290 11.4.2 Poloxamer-functionalised Magnetic Nanoparticles 291 11.4.3 Other TRP-functionalised Magnetic Nanoparticles 293 11.4.4 Summary 293 11.5 Conclusions 294 References 294 12 Temperature-responsive Polymers for Tissue Engineering 301 Kenichi Nagase, Masayuki Yamato, and Teruo Okano 12.1 Introduction 301 12.1.1 Thermo-responsive Cell Culture Dishes and Cell Sheets 301 12.1.2 Thermo-responsive Cell Culture Dishes Prepared by Electron-beam-induced Polymerization 302 12.1.3 Thermo-responsive Cell Culture Dishes for Enhancing Cell Adhesion and Proliferation by Immobilized Biological Ligands 303 12.1.4 Thermo-responsive Cell Culture Dish Prepared by Living Radical Polymerization 304 12.1.5 Patterned Thermo-responsive Cell Culture Substrates 306 12.1.6 Thermo-responsive Surfaces for Cell Separation 309 12.2 Conclusions 309 Acknowledgments 309 References 311 13 Thermogel Polymers for Injectable Drug Delivery Systems 313 VidhiM. Shah, Duc X. Nguyen, Deepa A. Rao, Raid G. Alany, and AdamW.G. Alani 13.1 Introduction 313 13.2 Pluronics® 314 13.3 Polyester-based Polymers 315 13.4 Chitosan and Derivatives 317 13.5 Polypeptides 318 13.6 Clinical Application of Thermogel Polymers 319 13.6.1 Ocular Delivery 319 13.6.2 Nasal Delivery 320 13.6.3 Antitumor Delivery/Drug Delivery Systems 321 13.7 Summary 323 References 323 14 Thermoresponsive Electrospun Polymer-based (Nano)fibers 329 Mariliz Achilleos and Theodora Krasia-Christoforou 14.1 Introduction 329 14.2 Basic Principles of Electrospinning 330 14.3 PNIPAM-based Electrospun (Nano)fibers 332 14.3.1 Temperature-triggered Wettability 332 14.3.2 Biomedicine 335 14.3.2.1 Drug Delivery 336 14.3.2.2 Tissue Engineering 339 14.3.2.3 Biosensing 341 14.3.2.4 Solid-phase Microextraction 341 14.3.2.5 Molecular Recognition 342 14.3.2.6 Organic–Inorganic PNIPAM-based Electrospun (Nano)fibers 342 14.3.3 Sensing 343 14.3.4 Other Applications 344 14.4 Other Types of Thermoresponsive Electrospun (Nano)fibers 345 14.5 Conclusions and Outlook 348 References 348 15 Catalysis by Thermoresponsive Polymers 357 Natalya A. Dolya and Sarkyt E. Kudaibergenov 15.1 Introduction 357 15.2 Metal Complexes Immobilized Within Thermosensitive Polymers 358 15.3 Thermoresponsive Polyampholytes 358 15.4 Thermosensitive Hydrogels in Catalysis 361 15.5 Thermoresponsive Catalytically Active Nano- and Microgels, Spheres, Capsules, and Micelles 364 15.6 Thermosensitive Self-Assemblies 367 15.7 Mono- and Bimetallic Nanoparticles Stabilized by Thermoresponsive Polymers 368 15.8 Enzymes-Embedded Thermoresponsive Polymers 369 15.9 Immobilization of Magnetic Nanoparticles into the Matrix of Thermoresponsive Polymers for Efficient Separation of Catalysts 369 15.10 Summary 370 Acknowledgments 371 References 371 Index 379

About the Author :
Edited by: Vitaliy V. Khutoryanskiy, Ph.D., is Professor of Formulation Science, Reading School of Pharmacy, University of Reading, Whiteknights, Reading, UK. Theoni K. Georgiou, Ph.D., is a Senior Lecturer in Polymer Chemistry, Department of Materials, Imperial College London, UK.