Temperature-Responsive Polymers

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
Jirí Spevácek

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