Tài liệu Handbook of Biodegradable Polymers

Contents
Preface XV
List of Contributors XVII
1 Polyesters 1
Adam L. Sisson, Michael Schroeter, and Andreas Lendlein
1.1 Historical Background 1
1.1.1 Biomedical Applications 1
1.1.2 Poly(Hydroxycarboxylic Acids) 2
1.2 Preparative Methods 3
1.2.1 Poly(Hydroxycarboxylic Acid) Syntheses 3
1.2.2 Metal-Free Synthetic Processes 6
1.2.3 Polyanhydrides 6
1.3 Physical Properties 7
1.3.1 Crystallinity and Thermal Transition Temperatures 7
1.3.2 Improving Elasticity by Preparing Multiblock Copolymers 9
1.3.3 Covalently Crosslinked Polyesters 11
1.3.4 Networks with Shape-Memory Capability 11
1.4 Degradation Mechanisms 12
1.4.1 Determining Erosion Kinetics 12
1.4.2 Factors Affecting Erosion Kinetics 13
1.5 Beyond Classical Poly(Hydroxycarboxylic Acids) 14
1.5.1 Alternate Systems 14
1.5.2 Complex Architectures 15
1.5.3 Nanofabrication 16
References 17
2 Biotechnologically Produced Biodegradable Polyesters 23
Jaciane Lutz Ienczak and Gláucia Maria Falcão de Aragão
2.1 Introduction 23
2.2 History 24
2.3 Polyhydroxyalkanoates – Granules Morphology 26
2.4 Biosynthesis and Biodegradability of Poly(3-Hydroxybutyrate) and
Other Polyhydroxyalkanoates 29
2.4.1 Polyhydroxyalkanoates Biosynthesis on Microorganisms 29
2.4.2 Plants as Polyhydroxyalkanoates Producers 32
2.4.3 Microbial Degradation of Polyhydroxyalkanoates 33
2.5 Extraction and Recovery 34
2.6 Physical, Mechanical, and Thermal Properties of
Polyhydroxyalkanoates 36
2.7 Future Directions 37
References 38
3 Polyanhydrides 45
Avi Domb, Jay Prakash Jain, and Neeraj Kumar
3.1 Introduction 45
3.2 Types of Polyanhydride 46
3.2.1 Aromatic Polyanhydrides 46
3.2.2 Aliphatic–Aromatic Polyanhydrides 49
3.2.3 Poly(Ester-Anhydrides) and Poly(Ether-Anhydrides) 49
3.2.4 Fatty Acid-Based Polyanhydrides 49
3.2.5 RA-Based Polyanhydrides 49
3.2.6 Amino Acid-Based Polyanhydrides 51
3.2.7 Photopolymerizable Polyanhydrides 52
3.2.8 Salicylate-Based Polyanhydrides 53
3.2.9 Succinic Acid-Based Polyanhydrides 54
3.2.10 Blends 55
3.3 Synthesis 55
3.4 Properties 58
3.5 In Vitro Degradation and Erosion of Polyanhydrides 63
3.6 In Vivo Degradation and Elimination of Polyanhydrides 64
3.7 Toxicological Aspects of Polyanhydrides 65
3.8 Fabrication of Delivery Systems 67
3.9 Production and World Market 68
3.10 Biomedical Applications 68
References 71
4 Poly(Ortho Esters) 77
Jorge Heller4.1 Introduction 77
4.2 POE II 79
4.2.1 Polymer Synthesis 79
4.2.1.1 Rearrangement Procedure Using an Ru(PPh3)3Cl2 Na2CO3
Catalyst 80
4.2.1.2 Alternate Diketene Acetals 80
4.2.1.3 Typical Polymer Synthesis Procedure 80
4.2.2 Drug Delivery 81
4.2.2.1 Development of Ivermectin Containing Strands to Prevent Heartworm
Infestation in Dogs 81
4.2.2.2 Experimental Procedure 81
4.2.2.3 Results 82
4.3 POE IV 82
4.3.1 Polymer Synthesis 82
4.3.1.1 Typical Polymer Synthesis Procedure 82
4.3.1.2 Latent Acid 83
4.3.1.3 Experimental Procedure 83
4.3.2 Mechanical Properties 83
4.4 Solid Polymers 86
4.4.1 Fabrication 86
4.4.2 Polymer Storage Stability 87
4.4.3 Polymer Sterilization 87
4.4.4 Polymer Hydrolysis 88
4.4.5 Drug Delivery 91
4.4.5.1 Release of Bovine Serum Albumin from Extruded Strands 91
4.4.5.2 Experimental Procedure 93
4.4.6 Delivery of DNA Plasmid 93
4.4.6.1 DNA Plasmid Stability 94
4.4.6.2 Microencapsulation Procedure 94
4.4.7 Delivery of 5-Fluorouracil 95
4.5 Gel-Like Materials 96
4.5.1 Polymer Molecular Weight Control 96
4.5.2 Polymer Stability 98
4.5.3 Drug Delivery 99
4.5.3.1 Development of APF 112 Mepivacaine Delivery System 99
4.5.3.2 Formulation Used 99
4.5.4 Preclinical Toxicology 100
4.5.4.1 Polymer Hydrolysate 100
4.5.4.2 Wound Instillation 100
4.5.5 Phase II Clinical Trial 100
4.5.6 Development of APF 530 Granisetron Delivery System 100
4.5.6.1 Preclinical Toxicology 100
4.5.6.2 Rat Study 101
4.5.6.3 Dog Study 101
4.5.6.4 Phase II and Phase III Clinical Trials 101
4.6 Polymers Based on an Alternate Diketene Acetal 102
4.7 Conclusions 104
References 104
5 Biodegradable Polymers Composed of Naturally Occurring
α-Amino Acids 107
Ramaz Katsarava and Zaza Gomurashvili
5.1 Introduction 107
5.2 Amino Acid-Based Biodegradable Polymers (AABBPs) 109
5.2.1 Monomers for Synthesizing AABBPs 109
5.2.1.1 Key Bis-Nucleophilic Monomers 109
5.2.1.2 Bis-Electrophiles 111
5.2.2 AABBPs’ Synthesis Methods 111
5.2.3 AABBPs: Synthesis, Structure, and Transformations 115
5.2.3.1 Poly(ester amide)s 115
5.2.3.2 Poly(ester urethane)s 119
5.2.3.3 Poly(ester urea)s 119
5.2.3.4 Transformation of AABBPs 119
5.2.4 Properties of AABBPs 121
5.2.4.1 MWs, Thermal, Mechanical Properties, and Solubility 121
5.2.4.2 Biodegradation of AABBPs 121
5.2.4.3 Biocompatibility of AABBPs 123
5.2.5 Some Applications of AABBPs 124
5.2.6 AABBPs versus Biodegradable Polyesters 125
5.3 Conclusion and Perspectives 126
References 127
6 Biodegradable Polyurethanes and Poly(ester amide)s 133
Alfonso Rodríguez-Galán, Lourdes Franco, and Jordi Puiggalí
Abbreviations 133
6.1 Chemistry and Properties of Biodegradable Polyurethanes 134
6.2 Biodegradation Mechanisms of Polyurethanes 140
6.3 Applications of Biodegradable Polyurethanes 142
6.3.1 Scaffolds 142
6.3.1.1 Cardiovascular Applications 143
6.3.1.2 Musculoskeletal Applications 143
6.3.1.3 Neurological Applications 144
6.3.2 Drug Delivery Systems 144
6.3.3 Other Biomedical Applications 145
6.4 New Polymerization Trends to Obtain Degradable Polyurethanes 145
6.4.1 Polyurethanes Obtained without Using Diisocynates 145
6.4.2 Enzymatic Synthesis of Polyurethanes 146
6.4.3 Polyurethanes from Vegetable Oils 147
6.4.4 Polyurethanes from Sugars 147
6.5 Aliphatic Poly(ester amide)s: A Family of Biodegradable
Thermoplastics with Interest as New Biomaterials 149
Acknowledgments 152
References 152
7 Carbohydrates 155
Gerald Dräger, Andreas Krause, Lena Möller, and Severian Dumitriu
7.1 Introduction 155
7.2 Alginate 156
7.3 Carrageenan 160
7.4 Cellulose and Its Derivatives 162
7.5 Microbial Cellulose 164
7.6 Chitin and Chitosan 165
7.7 Dextran 169
7.8 Gellan 171
7.9 Guar Gum 174
7.10 Hyaluronic Acid (Hyaluronan) 176
7.11 Pullulan 180
7.12 Scleroglucan 182
7.13 Xanthan 184
7.14 Summary 186
Acknowledgments 187
In Memoriam 187
References 187
8 Biodegradable Shape-Memory Polymers 195
Marc Behl, Jörg Zotzmann, Michael Schroeter, and Andreas Lendlein
8.1 Introduction 195
8.2 General Concept of SMPs 197
8.3 Classes of Degradable SMPs 201
8.3.1 Covalent Networks with Crystallizable Switching Domains,
Ttrans = Tm 202
8.3.2 Covalent Networks with Amorphous Switching Domains,
Ttrans = Tg 204
8.3.3 Physical Networks with Crystallizable Switching Domains,
Ttrans = Tm 205
8.3.4 Physical Networks with Amorphous Switching Domains,
Ttrans = Tg 208
8.4 Applications of Biodegradable SMPs 209
8.4.1 Surgery and Medical Devices 209
8.4.2 Drug Release Systems 210
References 212
9 Biodegradable Elastic Hydrogels for Tissue Expander Application 217
Thanh Huyen Tran, John Garner, Yourong Fu, Kinam Park, and
Kang Moo Huh
9.1 Introduction 217
9.1.1 Hydrogels 217
9.1.2 Elastic Hydrogels 217
9.1.3 History of Elastic Hydrogels as Biomaterials 218
9.1.4 Elasticity of Hydrogel for Tissue Application 219
9.2 Synthesis of Elastic Hydrogels 220
9.2.1 Chemical Elastic Hydrogels 220
9.2.1.1 Polymerization of Water-Soluble Monomers in the Presence of
Crosslinking Agents 220
9.2.1.2 Crosslinking of Water-Soluble Polymers 221
9.2.2 Physical Elastic Hydrogels 222
9.2.2.1 Formation of Physical Elastic Hydrogels via Hydrogen Bonding 22
9.2.2.2 Formation of Physical Elastic Hydrogels via
Hydrophobic Interaction 224
9.3 Physical Properties of Elastic Hydrogels 225
9.3.1 Mechanical Property 225
9.3.2 Swelling Property 227
9.3.3 Degradation of Biodegradable Elastic Hydrogels 229
9.4 Applications of Elastic Hydrogels 229
9.4.1 Tissue Engineering Application 229
9.4.2 Application of Elastic Shape-Memory Hydrogels as Biodegradable
Sutures 230
9.5 Elastic Hydrogels for Tissue Expander Applications 231
9.6 Conclusion 233
References 234
10 Biodegradable Dendrimers and Dendritic Polymers 237
Jayant Khandare and Sanjay Kumar
10.1 Introduction 237
10.2 Challenges for Designing Biodegradable Dendrimers 240
10.2.1 Is Biodegradation a Critical Measure of Biocompatibility? 243
10.3 Design of Self-Immolative Biodegradable Dendrimers 245
10.3.1 Clevable Shells – Multivalent PEGylated Dendrimer for
Prolonged Circulation 246
10.3.1.1 Polylysine-Core Biodegradable Dendrimer Prodrug 250
10.4 Biological Implications of Biodegradable Dendrimers 256
10.5 Future Perspectives of Biodegradable Dendrimers 259
10.6 Concluding Remarks 259
References 260
11 Analytical Methods for Monitoring Biodegradation Processes
of Environmentally Degradable Polymers 263
Maarten van der Zee
11.1 Introduction 263
11.2 Some Background 263
11.3 Defi ning Biodegradability 265
11.4 Mechanisms of Polymer Degradation 266
11.4.1 Nonbiological Degradation of Polymers 266
11.4.2 Biological Degradation of Polymers 267
11.5 Measuring Biodegradation of Polymers 267
11.5.1 Enzyme Assays 269
11.5.1.1 Principle 269
11.5.1.2 Applications 269
11.5.1.3 Drawbacks 270
11.5.2 Plate Tests 270
11.5.2.1 Principle 270
11.5.2.2 Applications 270
11.5.2.3 Drawbacks 270
1.5.3 Respiration Tests 271
11.5.3.1 Principle 271
11.5.3.2 Applications 271
11.5.3.3 Suitability 271
11.5.4 Gas (CO2 or CH4) Evolution Tests 272
11.5.4.1 Principle 272
11.5.4.2 Applications 272
11.5.4.3 Suitability 273
11.5.5 Radioactively Labeled Polymers 273
11.5.5.1 Principle and Applications 273
11.5.5.2 Drawbacks 273
11.5.6 Laboratory-Scale Simulated Accelerating Environments 274
11.5.6.1 Principle 274
11.5.6.2 Applications 274
11.5.6.3 Drawbacks 275
11.5.7 Natural Environments, Field Trials 275
11.6 Conclusions 275
References 276
12 Modeling and Simulation of Microbial Depolymerization Processes
of Xenobiotic Polymers 283
Masaji Watanabe and Fusako Kawai
12.1 Introduction 283
12.2 Analysis of Exogenous Depolymerization 284
12.2.1 Modeling of Exogenous Depolymerization 284
12.2.2 Biodegradation of PEG 287
12.3 Materials and Methods 287
12.3.1 Chemicals 287
12.3.2 Microorganisms and Cultivation 287
12.3.3 HPLC analysis 288
12.3.4 Numerical Study of Exogenous Depolymerization 288
12.3.5 Time Factor of Degradation Rate 291
12.3.6 Simulation with Time-Dependent Degradation Rate 293
12.4 Analysis of Endogenous Depolymerization 295
12.4.1 Modeling of Endogenous Depolymerization 295
12.4.2 Analysis of Enzymatic PLA Depolymerization 300
12.4.3 Simulation of an Endogenous Depolymerization
Process of PLA 302
12.5 Discussion 306
Acknowledgments 307
References 307
13 Regenerative Medicine: Reconstruction of Tracheal and Pharyngeal
Mucosal Defects in Head and Neck Surgery 309
Dorothee Rickert, Bernhard Hiebl, Rosemarie Fuhrmann, Friedrich Jung,
Andreas Lendlein, and Ralf-Peter Franke
14.4.3 Architecture of Scaffold 353
14.4.4 Barrier and Guidance Structure 354
14.5 Biodegradable Polymers for Tissue Engineering 354
14.5.1 Synthetic Polymers 355
14.5.2 Biopolymers 356
14.5.3 Calcium Phosphates 357
14.6 Some Examples for Clinical Application of Scaffold 357
14.6.1 Skin 357
14.6.2 Articular Cartilage 357
14.6.3 Mandible 358
14.6.4 Vascular Tissue 359
14.7 Conclusions 361
References 361
15 Drug Delivery Systems 363
Kevin M. Shakesheff
15.1 Introduction 363
15.2 The Clinical Need for Drug Delivery Systems 364
15.3 Poly(α-Hydroxyl Acids) 365
15.3.1 Controlling Degradation Rate 366
15.4 Polyanhydrides 368
15.5 Manufacturing Routes 370
15.6 Examples of Biodegradable Polymer Drug Delivery Systems
Under Development 371
15.6.1 Polyketals 371
15.6.2 Synthetic Fibrin 371
15.6.3 Nanoparticles 372
15.6.4 Microfabricated Devices 373
15.6.5 Polymer–Drug Conjugates 373
15.6.6 Responsive Polymers for Injectable Delivery 375
15.6.7 Peptide-Based Drug Delivery Systems 375
15.7 Concluding Remarks 376
References 376
16 Oxo-biodegradable Polymers: Present Status and
Future Perspectives 379
Emo Chiellini, Andrea Corti, Salvatore D’Antone, and David Mckeen Wiles
16.1 Introduction 379
16.2 Controlled – Lifetime Plastics 380
16.3 The Abiotic Oxidation of Polyolefi ns 382
16.3.1 Mechanisms 383
16.3.2 Oxidation Products 384
16.3.3 Prodegradant Effects 386
16.4 Enhanced Oxo-biodegradation of Polyolefi ns 387
16.4.1 Biodegradation of Polyolefi n Oxidation Products 390
16.4.2 Standard Tests 391
16.4.3 Biometric Measurements 393
16.5 Processability and Recovery of Oxo-biodegradable Polyolefi ns 395
16.6 Concluding Remarks 396
References 397
Index 399