Temperature-Responsive Polymers

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.

Auteur

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.

Contenu
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 ProteinPNIPAM Conjugates 16

1.6.2 PeptidePNIPAM Conjugates 18

1.6.3 Nucleic AcidPNIPAM 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 <p&...