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Bioinspired and Biomimetic Polymer Systems for Drug and Gene Delivery

Zhongwei Gu (Editor)
ISBN: 978-3-527-33420-9
360 pages
March 2015
Bioinspired and Biomimetic Polymer Systems for Drug and Gene Delivery (3527334203) cover image

Description

Here, front-line researchers in the booming field of nanobiotechnology describe the most promising approaches for bioinspired drug delivery, encompassing small molecule delivery, delivery of therapeutic proteins and gene delivery. The carriers surveyed include polymeric, proteinaceous and lipid systems on the nanoscale, with a focus on their adaptability for different cargoes and target tissues.
Thanks to the broad coverage of carriers as well as cargoes discussed, every researcher in the field will find valuable information here.
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Table of Contents

List of Contributors XIII

Preface XIX

1 Backbone Degradable and Coiled-Coil Based Macromolecular Therapeutics 1
Jiyuan Yang and Jindřich Kopeček

1.1 Introduction 1

1.2 Water-Soluble Polymers as Carriers of Anticancer Drugs 2

1.2.1 First Generation Conjugates – Design, Synthesis, and Activity 2

1.2.2 Analysis of Design Factors That Need Attention 2

1.2.2.1 Design of Conjugates for the Treatment of Noncancerous Diseases 2

1.2.2.2 Combination Therapy Using Polymer-Bound Therapeutics 3

1.2.2.3 New Targeting Strategies 4

1.2.2.4 Relationship Between Detailed Structure of the Conjugates and Their Properties 5

1.2.2.5 Impact of Binding a Drug to a Polymer on the Mechanism of Action 6

1.2.2.6 Mechanism of Internalization and Subcellular Trafficking 7

1.2.2.7 Relationship Between the Molecular Weight of the Carrier and the Efficacy of the Conjugate 7

1.2.3 Design of Second Generation Conjugates – Long-Circulating and Backbone Degradable 8

1.2.3.1 RAFT Copolymerization for the Synthesis of Conjugates 8

1.2.3.2 Click Reactions for Chain Extension into Multiblock Copolymers 10

1.2.3.3 Biological Properties of Long-Circulating Macromolecular Therapeutics 10

1.2.4 Summary of Part 2 and Future Prospects 14

1.3 Drug-Free Macromolecular Therapeutics – A New Paradigm in Drug Delivery 15

1.3.1 Biorecognition in Hybrid Polymer Systems 15

1.3.2 Coiled-Coils in Biomedical Systems 16

1.3.3 Coiled-Coil Based Drug-Free Macromolecular Therapeutics: Design, In Vitro, and In Vivo Activity 17

1.3.4 Potential, Limitations, and Future Prospect of Drug-Free Macromolecular Therapeutics 18

1.4 General Summary and Outlook 20

Acknowledgments 21

References 21

2 Dendritic Polymers as Targeting Nanoscale Drug Delivery Systems for Cancer Therapy 29
Kui Luo and Zhongwei Gu

2.1 Introduction 29

2.2 Functional Dendritic Polymers Based Drug Delivery Vehicles for Targeting Tumor Therapy via EPR Effect 30

2.2.1 Functional Dendritic Polymers for Encapsulation of Anticancer Drugs 32

2.2.2 Chemical Conjugation Functional Dendritic Polymers as Drug Delivery Systems 37

2.3 Tumor Targeting Moieties Functionalized Dendritic Drug Delivery Vehicles for Cancer Therapy 45

2.4 Conclusion 54

References 54

3 Composite Colloidal Nanosystems for Targeted Delivery and Sensing 61
Pilar Rivera Gil, Moritz Nazarenus, and Wolfgang J. Parak

3.1 Introduction 61

3.1.1 Working Toolkit 62

3.1.2 Engineering a Multifunctional Carrier 63

3.2 Objective 66

3.3 Cellular Behavior of the Carrier 66

3.3.1 Intracellular Fate 66

3.3.2 Biocompatibility 69

3.4 Applications 71

3.4.1 Delivery with Multifunctional PEM Capsules 71

3.4.1.1 Magnetic Targeting and Magnetofection 71

3.4.1.2 Strategies for Controlled Opening 73

3.4.2 Intracellular Ion Sensing 75

3.5 Conclusions 77

Abbreviations 77

References 78

4 Polymeric Micelles for Cancer-Targeted Drug Delivery 85
Huabing Chen, Zhishen Ge, and Kazunori Kataoka

4.1 Introduction 85

4.2 Micelle Formulations in Clinical Development 85

4.3 Particle Size of Micelles 89

4.4 Morphology of Micelles 92

4.5 Targeting Design of Micelles for Enhanced Accumulation and Cell Internalization 94

4.6 Functional Designs of Micelles 96

4.7 Design of Micelles for Gene Delivery 99

4.8 Challenge and Future Perspective 103

References 104

5 Biomimetic Polymers for In Vivo Drug Delivery 109
Wenping Wang and Kinam Park

5.1 Introduction 109

5.2 Commonly Used Biomimetic Polymers and Their Applications in DDS 110

5.2.1 Polylactones and Their Modifications 110

5.2.1.1 Poly(lactic acid) (PLA) 110

5.2.1.2 Poly(lactic-co-glycolic acid) (PLGA) 113

5.2.1.3 Poly(ε-caprolactone) (PCL) 118

5.2.2 Dendrimer 124

5.2.2.1 Structure and Properties of Dendrimers 124

5.2.2.2 Types of Dendrimers 124

5.2.2.3 Applications of Dendrimers as Carriers in Drug Delivery Systems 124

5.2.3 Synthetic Polypeptides 134

5.3 Challenges and Perspectives 135

References 136

6 Drug Delivery from Protein-Based Nanoparticles 149
Dan Ding and Xiqun Jiang

6.1 Introduction 149

6.2 Preparation of Protein-Based Nanoparticles 150

6.2.1 Desolvation 150

6.2.2 Emulsification 151

6.2.3 Coacervation 151

6.2.4 Polymer–Monomer Pair Reaction System 151

6.3 Drug Delivery from Albumin-Based Nanoparticles 152

6.3.1 Albumin-Based Nanoparticles as Drug Carriers 152

6.3.2 Targeting Ligand-Functionalized Albumin-Based Nanoparticles 154

6.3.3 Nanoparticle Albumin-Bound (nab) Technology 156

6.4 Drug Delivery from Gelatin-Based Nanoparticles 156

6.4.1 Gelatin-Based Nanoparticles as Drug Carriers 158

6.4.2 Targeting Ligand-Functionalized Gelatin-Based Nanoparticles 160

6.4.3 Site-Specific Drug Delivery System 162

6.5 Drug Delivery from Other Protein-Based Nanoparticles 163

References 165

7 Polymeric Gene Carriers 171
Xuesi Chen, Huayu Tian, and Xiuwen Guan

7.1 Gene Therapy and Gene Carriers 171

7.1.1 Gene Therapy 171

7.1.1.1 The Concept of Gene Therapy 171

7.1.1.2 Development and the Present Situation of Gene Therapy 171

7.1.1.3 Methods and Strategies of Gene Therapy 172

7.1.1.4 Research Contents and Challenges of Gene Therapy 174

7.1.2 Gene Carriers 175

7.1.2.1 The Concept of Gene Carrier 175

7.1.2.2 The Necessity of the Gene Carrier 175

7.1.2.3 Requirements of Gene Carrier 176

7.1.2.4 Classification of Gene Carrier 176

7.2 Polymeric Gene Carriers 178

7.2.1 Cationic Polymer Gene Carriers 178

7.2.1.1 Process of the Polycation Vector Mediated Gene Delivery 179

7.2.1.2 Categories and Research Situation of the Cationic Polymer Gene Vector 180

7.3 PEI Grafting Modification Polymeric Gene Carriers 183

7.3.1 Amino Acid Derivatives Modified Polymeric Gene Carriers 183

7.3.1.1 Poly(glutamic acid) Derivatives Modified PEI 184

7.3.1.2 Polyphenylalanine Derivatives Modified PEI 186

7.3.2 PEG Modified Hyperbranched PEI 187

7.4 Low Molecular Weight (LWM) PEI Base Polymeric Gene Carriers 188

7.4.1 Crosslinked Polycations 188

7.4.1.1 Crosslinked Polycation OEI-CBA 188

7.4.1.2 Crosslinked Polycation OEI-PBLG-PEGDA 189

7.4.1.3 Hexachlorotriphosphazene Crosslinked Polycation 190

7.4.2 Grafted Polycations 190

7.4.2.1 Grafted Cationic Polymer MP-g-OEI 190

7.4.2.2 Graft Cationic Polymer N-PAE-g-OEI 191

7.4.2.3 Graft Cationic Polymer mPEG-b-PMCC-g-OEI 192

7.5 Targeted Shielding System for Polymeric Gene Carriers 192

7.5.1 Static Shielding System 192

7.5.1.1 Poly(glutamine acid) Shielding System and PEGylations 195

7.5.1.2 Sulfonamides Related Shielding System 195

7.5.2 Other Design Strategies of Cationic Gene Carrier 196

7.6 Conclusion 197

References 197

8 pH-Sensitive Polymeric Nanoparticles as Carriers for Cancer Therapy and Imaging 203
Yi Li, Guang Hui Gao, Ick Chan Kwon, and Doo Sung Lee

8.1 Introduction 203

8.2 pH-Sensitive Polymers 204

8.2.1 pH-Sensitive Anionic Polymers 205

8.2.2 pH-Sensitive Cationic Polymers 207

8.2.3 pH-Sensitive Neutral Polymers 208

8.3 pH-Sensitive Polymers as Drug Carriers 209

8.3.1 pH-Sensitive Polymer–Drug Conjugates 210

8.3.2 pH-Sensitive Polymeric Micelles 210

8.3.3 pH-Sensitive Polymersomes 212

8.3.4 pH-Sensitive Polymer–Inorganic Hybrid Nanoparticles 214

8.3.5 pH-Sensitive Dendrimers 214

8.4 pH-Sensitive Polymers for Bioimaging 215

8.5 Conclusions 216

References 216

9 Charge-Reversal Polymers for Biodelivery 223
Bo Zhang, KaiWang, Jingxing Si, Meihua Sui, and Youqing Shen

9.1 Applications of Cationic Polymers in Biodelivery 223

9.2 Barriers for Cationic Polymers in In vitro and In vivo Applications 224

9.3 Characteristic pH Gradients in Tumor Interstitium and Endo/Lysosomes 225

9.4 Chemistry of Charge-Reversal Polymers Based on Acid-Labile Amides 226

9.4.1 pHe-Triggered Charge-Reversal 228

9.4.2 pHL-Triggered Charge-Reversal 229

9.5 Applications of Charge-Reversal Polymers in Biodelivery Systems 230

9.5.1 Charge-Reversal in Cancer Drug Delivery 230

9.5.2 Charge-Reversal in Gene Delivery 232

9.5.3 Charge-Reversal in Protein Delivery 235

9.5.4 Charge-Reversal Incorporated with Inorganic Materials 236

9.6 Perspectives 237

References 237

10 Phenylboronic Acid-Containing Glucose-Responsive Polymer Materials: Synthesis and Applications in Drug Delivery 243
Rujiang Ma and Linqi Shi

10.1 Introduction 243

10.2 PBA-Containing Polymers Operating Under Physiological Conditions 244

10.3 Chemically Crosslinked PBA-Based Gels 247

10.4 Self-Assembled PBA-Based Polymer Micelles 253

10.5 Self-Assembled PBA-Based Polymersomes 266

10.6 Perspectives 271

References 272

11 Extracellular pH-Activated Nanocarriers for Enhanced Drug Delivery to Tumors 277
You-Yong Yuan, Cheng-Qiong Mao, Jin-Zhi Du, Xian-Zhu Yang, and Jun Wang

11.1 Introduction 277

11.2 Passive and Active Tumor Targeting 278

11.3 Targeting the Extracellular pH (pHe) in Tumors 279

11.4 Extracellular pH-Induced Drug Delivery to Tumors 280

11.5 Ligand Exposure by a Shielding/Deshielding Method 281

11.6 Surface Charge Reversing Nanoparticles 283

11.6.1 Enhanced Cellular Uptake by Surface Charge Reversing Nanoparticles 283

11.6.2 Overcoming MDR by Surface Charge Reversing Nanoparticles 287

11.6.3 Enhanced Delivery of siRNA by Surface-Charge Reversing Nanoparticles 295

11.7 Conclusion 300

References 300

12 Stimulation-Sensitive Drug Delivery Systems 305
Xintao Shuai and Du Cheng

12.1 Introduction 305

12.2 pH-Sensitive Delivery Systems 306

12.2.1 pH-Sensitive Micellar Delivery Systems 306

12.2.2 pH-Sensitive Polymer–Drug Conjugates 307

12.2.3 pH-Sensitive Dendrimers 308

12.2.4 pH-Sensitive Liposomes 310

12.3 Thermo-Sensitive Delivery Systems 311

12.4 Biomolecule-Sensitive Delivery Systems 314

12.4.1 Enzyme-Sensitive Nanocarriers 315

12.4.2 Reduction–Responsive Conjugates 316

12.5 Other Environmentally Sensitive Nanocarriers 318

12.6 Outlook 319

References 320

Index 331

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Author Information

Professor Zhongwei Gu received his B. Sci. and M. Sci in Polymer Science from Peking University, prior to serving as a senior visiting scholar in the Research Triangle Institute, RTP and the University of Utah, respectively from 1984 to 1986 and 1991 to 1993. He was appointed as a professor in 1994, and presently serves as the chief scientist of the National Basic Research Program of China (the 973 program), director of the National Engineering Research Center for Biomaterials at Sichuan University, vice-chairman of the Chinese Society for Biomaterials (CSBM), executive member of the council of the Chinese Materials Research Society (C-MRS) and Chinese Society for Biomedical Engineering (CSBME) and is a Fellow of international Biomaterials Science and Engineering (FBSE).
His current research activities focus on the molecular design and controlled preparation of novel biomedical polymers, self-assembled biomaterials and nano-biomaterials, vectors for gene therapy, polymeric carriers and controlled drug delivery systems, biomaterials for molecular diagnosis, and biodegradable scaffolds for tissue engineering. Professor Zhongwei Gu has thrice being Chief Scientist of National Basic Research Program of China (National 973 Program) (1999-2004, 2005-2010, 2010-2015) and has being the PI of about 30 funding and research projects. Until now he has published more than 270 papers in Adv. Mater., Angew. Chem. Int. Ed., ACS Nano, Adv. Funct. Mater., Biomaterials, J. Control. Rel. and so on. He also has ~25 patents, composes/translates ~12 books and chapters, and is the invited speaker in many international and domestic conferences.
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