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Book Details
Abstract
The increased understanding of molecular aspects associated with chronic diseases, such as cancer and the role of tumor microenvironment, has led to the identification of endogenous and exogenous stimuli that can be exploited to devise “stimuli-responsive” materials for site-specific drug delivery applications. This book provides a comprehensive account on the design, materials chemistry, and application aspects behind these novel stimuli-responsive materials.
Setting the scene, the editors open with a chapter addressing the need for smart materials in delivery applications for therapy, imaging and disease diagnosis. The following chapter describes the key physical and chemical aspects of smart materials, from lipids to polymers to hybrid materials, providing the reader with a springboard to delve into the more application oriented chapters that follow. With in-depth coverage of key drug delivery systems such as pH-responsive, temperature responsive, enzyme-responsive and light responsive systems, this book provides a rigorous foundation to the field. A perfect resource for graduate students and newcomers, the closing chapter on regulatory and commercialization challenges also makes the book ideal for those wanting to take the next step towards clinical translation.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Cover | Cover | ||
| Stimuli-responsive Drug Delivery Systems | i | ||
| Preface | v | ||
| Dedication | vii | ||
| Contents | ix | ||
| Chapter 1 - Fundamentals of Stimuli-responsive Drug and Gene Delivery Systems | 1 | ||
| 1.1 Introduction | 1 | ||
| 1.2 pH-Sensitive DDS | 3 | ||
| 1.3 Redox Potential-sensitive DDS | 5 | ||
| 1.4 Enzyme-sensitive DDS | 7 | ||
| 1.5 Thermo-sensitive DDS | 9 | ||
| 1.6 Magnetically-sensitive DDS | 11 | ||
| 1.7 Ultrasound-sensitive DDS | 12 | ||
| 1.8 Light-sensitive DDS | 13 | ||
| 1.9 Stimuli-sensitive DDS for Combination Therapy: Case of Cancer | 18 | ||
| 1.10 Concluding Remarks | 18 | ||
| References | 24 | ||
| Chapter 2 - Materials and Chemistry of Stimuli-responsive Drug Delivery Systems | 33 | ||
| 2.1 Introduction | 33 | ||
| 2.2 Physical Stimuli | 34 | ||
| 2.2.1 Thermoresponsive Materials | 34 | ||
| 2.2.2 Photoresponsive Materials | 35 | ||
| 2.2.2.1 Photoisomerizable Groups | 35 | ||
| 2.2.2.2 Photo-cleavable Groups | 37 | ||
| 2.2.3 Magnetically Responsive Materials | 40 | ||
| 2.3 Chemical Stimuli | 41 | ||
| 2.3.1 pH Responsive Materials | 41 | ||
| 2.3.2 Thiol-responsive Materials | 43 | ||
| 2.4 Biological/Biochemical Stimuli | 44 | ||
| 2.5 Summary | 46 | ||
| References | 46 | ||
| Chapter 3 - pH-responsive Drug Delivery Systems | 51 | ||
| 3.1 Introduction | 51 | ||
| 3.1.1 pH Environment in Gastrointestinal Organs | 52 | ||
| 3.1.2 Acidic pH Environment in Pathological Tissues | 52 | ||
| 3.1.3 Acidic Subcellular Organelles | 52 | ||
| 3.2 Classification of pH-responsive Materials | 53 | ||
| 3.2.1 Polymers with Ionizable Functional Groups | 53 | ||
| 3.2.1.1 pH-responsive Acidic Polymers | 54 | ||
| 3.2.1.2 pH-responsive Basic Polymers | 55 | ||
| 3.2.1.3 pH-responsive Natural Polymers | 57 | ||
| 3.2.2 Acid-labile pH-sensitive Nanocarriers | 58 | ||
| 3.2.3 pH-responsive Inorganic Nanoscale Materials | 59 | ||
| 3.3 Release Mechanism of pH-responsive DDS | 59 | ||
| 3.3.1 Hydrophobic–Hydrophilic Transition Induced Disassembly | 60 | ||
| 3.3.2 Cleavage of Acid-labile Linkers for Drug Release | 61 | ||
| 3.3.3 Gel Swelling | 62 | ||
| 3.3.4 Cap/Coating Removal | 63 | ||
| 3.3.5 Gas Generation | 63 | ||
| 3.4 pH-responsive DDS for Targeted Delivery | 64 | ||
| 3.4.1 PEG Shedding | 64 | ||
| 3.4.2 Ligand Shielding/Deshielding | 66 | ||
| 3.4.3 Ligand Pop-up Targeting | 66 | ||
| 3.4.4 Charge Reversal | 68 | ||
| 3.4.5 Size Change | 68 | ||
| 3.4.6 Membrane Fusion by pH-sensitive Peptides | 70 | ||
| 3.4.6.1 pH-(Low) Insertion Peptide (pHLIP) | 70 | ||
| 3.4.6.2 pH-activatable Cell-penetrating Peptides CPPs | 71 | ||
| 3.5 pH-responsive DDS for Intracellular Delivery | 71 | ||
| 3.6 Conclusions | 75 | ||
| References | 75 | ||
| Chapter 4 - Thermo-responsive Nanomedicines for Drug Delivery in the Gastrointestinal Tract | 83 | ||
| 4.1 Introduction | 83 | ||
| 4.2 Gastrointestinal Tract | 85 | ||
| 4.2.1 Constitution of the Gastrointestinal Tract | 85 | ||
| 4.2.2 Differences Between Normal and Diseased Tissues | 86 | ||
| 4.2.3 Inflammatory Bowel Disease | 89 | ||
| 4.2.4 Gastric and Colorectal Cancer | 90 | ||
| 4.3 Thermo-responsive Materials and Nanocarrier Systems | 90 | ||
| 4.3.1 Thermo-responsive Polymeric Nanoparticles | 94 | ||
| 4.3.2 Thermo-responsive Liposomes | 98 | ||
| 4.3.3 Thermo-responsive Micelles | 101 | ||
| 4.4 Conclusions and Future Perspectives | 103 | ||
| Acknowledgements | 103 | ||
| References | 104 | ||
| Chapter 5 - Redox-responsive Drug Delivery Systems | 109 | ||
| 5.1 Redox-responsive Drug Delivery Systems | 109 | ||
| 5.1.1 Redox Profile of the Tumor Microenvironment and the Cancer Cell | 111 | ||
| 5.1.1.1 Reactive Oxygen Species | 111 | ||
| 5.1.1.2 Glutathione | 112 | ||
| 5.1.1.3 Redox Potential in Cancer Cell | 113 | ||
| 5.1.2 Reduction (Glutathione)-responsive Systems | 114 | ||
| 5.1.2.1 Nanogels | 114 | ||
| 5.1.2.2 Amphiphilic Copolymer Nanomicellar Systems | 117 | ||
| 5.1.2.3 Lipid-based Nanocarriers | 122 | ||
| 5.1.2.4 Vesicles: Liposomes and Polymersomes | 124 | ||
| 5.1.2.5 Mesoporous Silica Nanoparticles | 126 | ||
| 5.1.2.6 Gold Nanoparticles | 127 | ||
| 5.1.2.7 Magnetic Iron Oxide Nanoparticles | 128 | ||
| 5.1.3 ROS-responsive Systems | 129 | ||
| 5.1.3.1 Sulphur as Oxidative Stress Responsive Agent for Nanoparticles | 129 | ||
| 5.1.3.2 Selenium Linker/Crosslink as a ROS Responsive Agent for Amphiphilic Nanoparticles | 132 | ||
| 5.1.3.3 Boronic Ester Oxidation by ROS Triggered Drug Release | 132 | ||
| 5.1.3.4 Double Stimuli: Intrinsic ROS and External Light | 133 | ||
| 5.1.3.5 Immunotherapy | 134 | ||
| 5.1.4 Dual ROS–GSH Redox Responsive Systems | 136 | ||
| 5.1.5 New Avenues in Redox Responsive Drug Release | 138 | ||
| 5.1.5.1 The Increase ROS and Decrease GSH Strategy | 138 | ||
| 5.1.5.2 Intracellular GSH-triggered ROS Production | 140 | ||
| References | 141 | ||
| Chapter 6 - Magnetically-responsive DDS | 145 | ||
| 6.1 Introduction | 145 | ||
| 6.2 Synthesis and Heating Mechanism | 146 | ||
| 6.3 Applications of Magnetically-sensitive Nanoparticles as Drug Delivery Systems | 149 | ||
| 6.4 Hot Spot Effect Adds to Chemotherapy | 155 | ||
| 6.5 Conclusion | 158 | ||
| Acknowledgements | 159 | ||
| References | 159 | ||
| Chapter 7 - Light-responsive Drug Delivery Systems | 163 | ||
| 7.1 Introduction | 163 | ||
| 7.2 Light-responsive Organic Nanomaterials | 165 | ||
| 7.2.1 Drug Release by Photo-induced Bond Cleavage | 165 | ||
| 7.2.2 Drug Release by Photo-induced Chemical Structure Change | 170 | ||
| 7.2.3 Conjugated Polymers | 174 | ||
| 7.3 Inorganic Nanomaterials for Photothermal Drug Delivery | 175 | ||
| 7.3.1 Metallic NPs | 176 | ||
| 7.3.2 Carbon-based Nanomaterials | 178 | ||
| 7.4 NIR Light-responsive Organic-inorganic Hybrid Materials | 180 | ||
| 7.4.1 Surface-modified Photoluminescent Inorganic Nanomaterials | 181 | ||
| 7.4.2 Nanomaterial-dispersed Hydrogel | 182 | ||
| 7.5 Conclusion | 186 | ||
| References | 187 | ||
| Chapter 8 - Integrated Polymer Composites for Electro-responsive Drug Delivery | 192 | ||
| 8.1 Introduction | 192 | ||
| 8.2 An Ideal Electroresponsive Hydrogel Device | 195 | ||
| 8.3 Recent Advances in Electroresponsive Drug Delivery: Representative and Leading Examples | 196 | ||
| 8.3.1 Polymer-carbon Nanotube Composites | 196 | ||
| 8.3.2 Polypyrrole Based Scaffolds | 200 | ||
| 8.3.3 Semi-conductive, Polymer-Peptide-Hydrogel (PPH) Nanocomposite | 201 | ||
| 8.3.4 Smart Montmorillonite-polypyrrole Scaffolds | 201 | ||
| 8.3.5 Electrically Responsive Microreservoirs (ERMR) for Bone Tissue Engineering | 202 | ||
| 8.3.6 Peptide-conjugated Hydrogel Nanoparticles | 203 | ||
| 8.3.7 Reduced Graphene Oxide Composite Hydrogel | 203 | ||
| 8.4 Molecular mechanism(s) of Electro-actuable Drug Release | 204 | ||
| 8.5 Conclusions and Future Directions | 205 | ||
| Acknowledgements | 206 | ||
| References | 206 | ||
| Chapter 9 - Enzyme-responsive Drug Delivery Systems | 209 | ||
| 9.1 Introduction | 209 | ||
| 9.2 Oxidoreductase-sensitive Drug Delivery Systems | 210 | ||
| 9.3 Hydrolase-sensitive Drug Delivery Systems | 214 | ||
| 9.3.1 Proteases | 214 | ||
| 9.3.1.1 Matrix Metalloproteinases (MMPs) | 214 | ||
| 9.3.1.2 Other Proteases | 218 | ||
| 9.3.2 Esterases | 221 | ||
| 9.3.3 Glycosidases | 224 | ||
| 9.4 Summary | 226 | ||
| References | 226 | ||
| Chapter 10 - Swelling-controlled Drug Delivery Systems | 232 | ||
| 10.1 Introduction | 232 | ||
| 10.1.1 Polymers | 232 | ||
| 10.1.2 The Important Roles of Polymers in Drug Delivery | 233 | ||
| 10.1.2.1 Natural Polymers in Drug Delivery | 234 | ||
| 10.1.2.2 Synthetic Polymers in Drug Delivery | 235 | ||
| 10.2 Introduction to Swelling Controlled Drug Delivery Systems | 235 | ||
| 10.2.1 Structuring Polymers to Control Swelling Kinetics | 238 | ||
| 10.2.2 Cross-linking | 238 | ||
| 10.2.2.1 Definition and Classification of Polymeric Cross-links | 238 | ||
| 10.2.2.2 Effects of Polymeric Cross-linking on Swelling Controlled Kinetics | 239 | ||
| 10.2.2.3 Hydrophilicity | 239 | ||
| 10.2.2.4 Ionic Strength | 240 | ||
| 10.3 Drug Release Mechanism from Swelling Controlled Delivery Systems | 241 | ||
| 10.3.1 Drug Diffusion-controlled Release | 242 | ||
| 10.3.1.1 Monolithic Devices | 242 | ||
| 10.3.1.2 Reservoir Systems | 243 | ||
| 10.3.2 Polymer Relaxation-controlled Swelling | 245 | ||
| 10.3.3 Degradation-controlled Release | 246 | ||
| 10.4 Swellable Products | 247 | ||
| 10.4.1 Swellable Matrices | 247 | ||
| 10.4.1.1 Swelling Mechanism of Swellable Matrices | 247 | ||
| 10.4.1.2 Advantages of Swellable Matrices | 248 | ||
| 10.4.2 Superdisintegrants | 249 | ||
| 10.4.2.1 Ideal Superdisintegrants | 250 | ||
| 10.4.2.2 Method of Incorporation | 250 | ||
| 10.4.3 Swellable Devices | 251 | ||
| 10.5 Factors Influencing Drug Release in Swelling Controlled Systems | 252 | ||
| 10.5.1 Physical Properties of the Swelling Device | 252 | ||
| 10.5.2 Formulation Factors | 252 | ||
| 10.5.3 Drug-related Factors | 253 | ||
| 10.5.4 Drug Delivery System Geometry | 253 | ||
| 10.5.5 Degree of Swelling Agent Saturation | 253 | ||
| 10.5.6 Stimuli Responsive Release | 254 | ||
| 10.6 Mechanistic Mathematical Models for Predicting Drug Release | 254 | ||
| 10.7 Disadvantages of Swelling Controlled Systems | 259 | ||
| 10.8 Conclusion and Future Perspectives | 259 | ||
| References | 260 | ||
| Chapter 11 - Biologically-inspired Stimuli-responsive DDS | 265 | ||
| 11.1 Introduction | 265 | ||
| 11.2 Bio-inspired Synthetic Designs of DDS | 267 | ||
| 11.2.1 Bio-inspired Nanoscale Composites Architecture | 267 | ||
| 11.2.1.1 Layer-by-layer-NC-based Bioinspired DDS | 268 | ||
| 11.2.1.1.1\r2-D Metal-polymer Nanocomposites as LbL-DDS.Metal-polymer nanocomposites can lead to innovative 2-D hybrid structures, which are... | 269 | ||
| 11.2.1.1.2\rBio-inspired Janus Nanostructures for Smart DDS.More dynamic and complex material properties can result when the LbL-metal-polym... | 271 | ||
| 11.2.1.1.3\rBioinspired LbL-DDS-based Scaffolds.As one of the most important tools for tissue engineering, scaffolds are forged extracellula... | 273 | ||
| 11.2.1.1.4\rBio-inspired Printing Techniques Using LbL-DDS | 277 | ||
| 11.3 Challenges and Future Insights | 279 | ||
| References | 280 | ||
| Chapter 12 - Stimuli-responsive Materials in Theranostics | 284 | ||
| 12.1 Introduction | 284 | ||
| 12.2 Chemical and Biological Stimuli-sensitive Theranostic Systems | 285 | ||
| 12.2.1 pH-responsive Theranostic Systems | 285 | ||
| 12.2.1.1 pH Triggered Protonation | 287 | ||
| 12.2.1.2 Acid Labile Bond Cleavage | 287 | ||
| 12.2.2 Reduction-responsive Theranostic Systems | 290 | ||
| 12.2.3 Enzyme-responsive Theranostic Systems | 291 | ||
| 12.2.4 Multi-responsive Theranostic Systems | 292 | ||
| 12.3 Physically Stimuli-responsive Theranostic Systems | 292 | ||
| 12.3.1 Ultrasound-triggered Theranostic Systems | 292 | ||
| 12.3.2 Thermoresponsive Theranostic Systems | 298 | ||
| 12.3.3 Magnetic-responsive Theranostic Systems | 300 | ||
| 12.3.4 Light-responsive Theranostic Systems | 302 | ||
| 12.3.5 Electroresponsive Theranostic Systems | 305 | ||
| 12.4 Summary and Future Outlook | 307 | ||
| Acknowledgements | 307 | ||
| References | 307 | ||
| Chapter 13 - Stimuli-responsive Material Inspired Drug Delivery Systems and Devices | 317 | ||
| 13.1 Introduction | 317 | ||
| 13.2 pH-Responsive Drug Delivery Systems | 318 | ||
| 13.3 Glucose-triggered Drug Delivery Systems | 322 | ||
| 13.4 Enzyme-responsive Drug Delivery Devices | 323 | ||
| 13.5 Redox-sensitive Stomatocyte Nanomotors | 325 | ||
| 13.6 Magnetically Triggered Drug Delivery Devices | 327 | ||
| 13.7 Light Triggered Drug Delivery Devices | 329 | ||
| 13.8 Ultrasound Responsive Drug Delivery Vesicles | 330 | ||
| 13.9 Conclusions | 332 | ||
| Acknowledgements | 332 | ||
| References | 332 | ||
| Chapter 14 - Regulatory and Commercialization Challenges with Stimuli-responsive Nanomedicines | 335 | ||
| 14.1 Introduction | 335 | ||
| 14.2 Challenges with Developing Nanomedicines | 336 | ||
| 14.2.1 Controlling Physicochemical Properties | 337 | ||
| 14.2.2 Challenges with Analytical Characterization | 338 | ||
| 14.2.3 Manufacturing Challenges with Nanomaterials | 340 | ||
| 14.2.4 Challenges with Biological Characterization | 342 | ||
| 14.2.5 Challenges with Toxicological Profiling | 343 | ||
| 14.2.6 Challenges with Immunological Profiling | 345 | ||
| 14.3 Regulatory Framework and Nanomaterials | 346 | ||
| References | 352 | ||
| Subject Index | 355 |