Advances in Polymer Sciences Also Available Electronically 7
Aims and Scope 8
Preface 9
Contents 11
Polymeric Nanoparticles of Chitosan Derivatives as DNA and siRNA Carriers 13
1 Introduction 14
2 Parameters Affecting Transfection Efficiency of Chitosan/DNA Complexes or Gene Silencing of Chitosan/siRNA Complexes 15
3 Biological and Cellular Barriers to Gene Delivery 16
3.1 DNA or siRNA Condensation and Protection 16
3.2 Uptake by Target Cells 18
3.3 Endosomal Escape 18
3.4 Nuclear Targeting 19
4 Specific Ligand Modification of Chitosan 19
4.1 Galactose 19
4.2 Mannose 22
4.3 Folate 23
4.4 Transferrin 25
4.5 Epidermal Growth Factor and RGD 25
5 Modification of Buffering Capacity 26
5.1 Imidazole 26
5.2 Low-MW PEI 28
5.3 Methacrylic Acid 29
6 Summary 29
References 30
Chitosan and Its Derivatives for Drug Delivery Perspective 34
1 Introduction 35
2 Nanomaterials 36
2.1 Nanomaterials in Drug Delivery 36
3 Biopolymers in Drug Delivery 37
3.1 Alginate 37
3.2 Starch 39
3.3 Dextran 40
3.4 Pullulan 41
3.5 Chitosan 41
4 Chitosan Sources and Chemical Structure 42
4.1 Chemical Methodology for the Preparation of Chitosan 42
4.2 Physicochemical and Biological Properties of Chitosan 43
4.3 Limitations 43
4.4 Modification of Chitosan 43
4.4.1 Covalent Modifications 45
4.4.2 Polyelectrolyte Complexes 45
5 Methods for the Preparation of Nano/Microparticles of Chitosan 46
5.1 Emulsion Crosslinking 47
5.2 Coacervation/Precipitation 47
5.3 Spray Drying 47
5.4 Emulsion Droplet Coalescence Method 47
5.5 Ionic Gelation 47
5.6 Reverse Micellar Method 48
5.7 Seiving Method 48
6 Applications in Drug Delivery 48
6.1 Drug Delivery for Dental Diseases 48
6.2 Buccal Delivery Systems 50
6.3 Gastrointestinal Delivery 50
6.4 Colon-Specific Drug Delivery 51
6.5 Mucosal Vaccination 52
6.6 Gene Delivery 53
7 Chitosan and Its Derivatives 54
7.1 Hydrophobic Modification 54
7.2 Thiolation 56
7.3 Quaternized Chitosan 57
7.4 Chemical Grafting of Chitosan 59
8 Conclusion 60
References 60
Chitosan-Based Nanoparticles in Cancer Therapy 65
1 Introduction 67
2 Chitosan-Based Nanotechnology 67
3 Chitosan Nanoparticles in Cancer Therapy 68
3.1 Breast Cancer 69
3.2 Prostate Cancer 71
3.3 Lung Cancer 72
3.4 Ovarian Cancer 76
3.5 Pancreatic Cancer 80
3.6 Colon Cancer 82
3.7 Melanoma Cancer 86
3.8 Bladder Cancer 91
4 Conclusions 93
References 94
Chitosan and Thiolated Chitosan 102
1 Introduction 103
2 Synthesis of Thiolated Chitosans 105
2.1 Alkyl Thiolated Chitosans 105
2.2 Aryl Thiolated Chitosans 107
3 Properties of Thiolated Chitosans 107
3.1 Mucoadhesive Properties 107
3.2 In Situ Gelling Properties 108
3.3 Permeation-Enhancing Effect 109
3.4 Efflux Pump Inhibition 110
3.5 Transfection-Enhancing Properties 111
3.6 Controlled Drug Release Properties 112
3.7 Safety and Stability 113
4 Formulations 113
4.1 Microparticles and Nanoparticles 113
4.2 Matrix Tablets 114
5 In Vivo Studies: Proof of Concept 115
5.1 Oral Drug Delivery 115
5.2 Nasal Drug Delivery 116
5.3 Buccal Drug Delivery 117
6 Conclusions 117
References 118
Chitosan-Based Particulate Systems for Non-Invasive Vaccine Delivery 120
1 Introduction 121
2 Particulate Systems for Vaccine Delivery 122
3 Chitosan 123
3.1 Mode of Action 124
4 Mucosal Delivery 126
4.1 Oral Delivery 127
4.2 Nasal Delivery 131
4.3 Pulmonary Delivery 137
5 Transdermal and Intradermal Delivery 138
6 Parenteral Delivery 139
7 Concluding Remarks 140
References 141
Multifunctional Chitosan Nanoparticles for Tumor Imaging and Therapy 147
1 Introduction 148
2 Tumor-Targeted Delivery of Chitosan Nanoparticles 149
2.1 Passive Targeting (EPR Effects) 150
2.2 Active Targeting 151
3 In Vivo Tumor Imaging with Chitosan Nanoparticles 154
3.1 Optical Imaging 154
3.2 MR Imaging 156
4 Application for Tumor Therapy 158
4.1 Anticancer Drug Delivery 159
4.2 Photodynamic Therapy 160
4.3 Gene Delivery 163
5 Conclusion 165
References 166
Chitosan-Coated Iron Oxide Nanoparticles for Molecular Imaging and Drug Delivery 170
1 Introduction 171
2 Synthesis of IONP Cores 172
3 Synthesis of Chitosan-Coated IONPs 174
3.1 Chitosan 174
3.2 Synthesis of Chitosan-Coated IONPs 175
3.2.1 Ex Situ Coating Approaches 175
3.2.2 In Situ Coating Approaches 177
4 Applications of Chitosan-Coated IONPs for Molecular Imaging and Therapy 178
4.1 Chitosan-Coated IONP Cancer Targeting Strategies 178
4.2 Applications of Chitosan-Coated IONPs in Molecular Imaging 179
4.2.1 MR Imaging 180
4.2.2 Fluorescent Imaging 181
4.3 Drug Delivery 183
4.3.1 Drug Loading and Release 183
4.3.2 Chitosan-Based Magnetic Nanoparticles for Chemotherapeutic Delivery 184
4.3.3 Chitosan-Based Magnetic Nanoparticles for DNA and siRNA Delivery 185
5 Conclusions and Outlook 186
References 189
Chitosan: Its Applications in Drug-Eluting Devices 192
1 Introduction 193
2 Modification and/or Crosslinking of Chitosan 194
2.1 Chitosan Chemistry 194
2.1.1 Acylation 194
2.1.2 Quaternization 195
2.1.3 Sugar-Modification 196
2.1.4 Carboxymethylation 197
2.1.5 Sulfation 198
2.1.6 Thiolation 199
2.2 Ionic Modification 202
2.3 Modification by Aldehydes 202
2.4 Modification by Genipin 203
2.5 Modification by Other Crosslinking Agents 204
3 Drug-Eluting Stents 206
3.1 Eluting Coating for Metallic Stents 207
3.2 Eluting Membrane for Metallic Stents 210
3.3 Polymeric Stent Crosslinked by an Epoxy Compound 211
3.4 Polymeric Stent Crosslinked by Genipin 218
4 Drug-Eluting Medical Devices 219
4.1 Wound Dressings and Artificial Skin 220
4.2 Cartilage Graft 222
4.3 Bone Graft 223
4.4 Nerve Guidance Conduit 225
5 Conclusions 227
References 227
Index 238