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Book Details
Abstract
Nanomedicines and nanopharmacology is a rapidly developing and evolving field with new techniques and applications under constant development. This book will provide an overview of the chemistry of nanocarrier design and the considerations that need to be made when developing a nanomedicine. Providing an understanding of the relationship of nanocarrier, drug and targetting moieties and physico-chemical properties, this title will provide an accurate and current representation of the field by addressing the promises, prospects and pitfalls of nanomedicine. Covering a wide range of areas in detail, this book will provide an excellent companion for medicinal chemists, pharmacologists and biochemists working in industry or academia.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Cover | Cover | ||
| Contents | ix | ||
| Preface | vii | ||
| References | viii | ||
| Chapter 1 Design Considerations for Properties of Nanocarriers on Disposition and Efficiency of Drug and Gene Delivery | 1 | ||
| 1.1 Introduction | 1 | ||
| 1.2 Types of Nanocarriers/Nanoparticles | 2 | ||
| 1.2.1 Viral Nanoparticles (VNPs) | 2 | ||
| 1.2.2 Micelles and Liposomes | 2 | ||
| 1.2.3 Polymeric Nanoparticles | 4 | ||
| 1.2.4 Dendritic Nanoparticles | 5 | ||
| 1.2.5 Peptidic Nanoparticles | 6 | ||
| 1.2.6 Nanocrystals and Nanosuspensions | 7 | ||
| 1.2.7 Metallic Nanoparticles | 7 | ||
| 1.2.8 Silica Nanoparticles | 8 | ||
| 1.2.9 Carbon-based Nanoparticles | 8 | ||
| 1.3 Physicochemical Factors that Affect Nanoparticle Efficiency | 8 | ||
| 1.3.1 Size | 10 | ||
| 1.3.2 Shape | 11 | ||
| 1.3.3 Surface Charge | 11 | ||
| 1.3.4 Ligands | 12 | ||
| 1.4 Conclusions | 13 | ||
| References | 14 | ||
| Chapter 2 Targeting Cyclins and Cyclin-dependent Kinases Involved in Cell Cycle Regulation by RNAi as a Potential Cancer Therapy | 23 | ||
| 2.1 Introduction | 23 | ||
| 2.2 The Cell Cycle | 24 | ||
| 2.2.1 An Overview | 24 | ||
| 2.2.2 Restriction Points and Checkpoints | 26 | ||
| 2.2.3 Regulation of Cell Cycle | 27 | ||
| 2.3 Deregulation of the Cell Cycle in Cancer | 28 | ||
| 2.3.1 Conventional Drug Therapy Against Cyclins and CDK Inhibitors | 29 | ||
| 2.4 RNA Interference | 29 | ||
| 2.4.1 Mechanism of Action | 29 | ||
| 2.4.2 RNAi and Cell Cycle Proteins | 30 | ||
| 2.4.3 Overcoming RNAi Intended for Cell Cycle Regulation | 36 | ||
| 2.5 Concluding Remarks | 38 | ||
| Acknowledgments | 39 | ||
| References | 39 | ||
| Chapter 3 Nanoparticle Carriers to Overcome Biological Barriers to siRNA Delivery | 46 | ||
| 3.1 Introduction | 46 | ||
| 3.1.1 In Vitro siRNA Delivery | 48 | ||
| 3.1.2 In Vivo siRNA Delivery | 66 | ||
| 3.2 Extracellular Barriers | 66 | ||
| 3.2.1 Surviving Degradation in the Systemic Circulation | 68 | ||
| 3.2.2 Escaping the Immune System | 69 | ||
| 3.2.3 Exiting the Systemic Circulation at the Site of Action | 70 | ||
| 3.2.4 Extracellular Matrix | 73 | ||
| 3.3 Cellular Barriers | 74 | ||
| 3.3.1 Binding to the Cell Membrane | 74 | ||
| 3.3.2 Entering the Cell | 77 | ||
| 3.3.3 Permeating the Lipid Bilayer of Endosomes | 78 | ||
| 3.3.4 Intra-cytoplasmic Trafficking | 79 | ||
| 3.4 siRNA Delivery Systems | 80 | ||
| 3.4.1 Lipid-based Delivery Systems | 81 | ||
| 3.4.2 Polymer-based Delivery Systems | 82 | ||
| 3.4.3 Peptides | 84 | ||
| 3.4.4 Recent Accomplishments in siRNA Delivery | 85 | ||
| References | 90 | ||
| Chapter 4 Magnetic Targeting as a Vehicle for the Delivery of Nanomedicines | 106 | ||
| 4.1 Introduction | 106 | ||
| 4.2 External Magnetic Device | 107 | ||
| 4.3 Labeling Mesenchymal Stem Cells with Supraparamagnetic Iron Oxide | 107 | ||
| 4.3.1 Cell Proliferation | 109 | ||
| 4.3.2 Multipotential Differentiation Capacity | 110 | ||
| 4.4 Adhesion of m-MSCs to the Tissue Injured Site | 112 | ||
| 4.4.1 Cell Adhesion Rate in Ex vivo Studies | 112 | ||
| 4.4.2 Cell Distribution (Bioluminescence Imaging) | 112 | ||
| 4.5 Animal Studies | 114 | ||
| 4.5.1 Cartilage Regeneration | 114 | ||
| 4.5.2 Bone Regeneration | 115 | ||
| 4.5.3 Muscle Regeneration | 116 | ||
| 4.6 Conclusion | 118 | ||
| Acknowledgments | 118 | ||
| References | 118 | ||
| Chapter 5 The Development of Theranostics - Imaging Considerations and Targeted Drug Delivery | 120 | ||
| 5.1 Introduction | 120 | ||
| 5.2 Theranostic Carrier Materials | 124 | ||
| 5.2.1 Polymeric Nanoparticles | 124 | ||
| 5.2.2 Liposomes | 129 | ||
| 5.2.3 Antibodies | 129 | ||
| 5.2.4 Metal Nanoparticles | 130 | ||
| 5.2.5 Nanocarbons | 131 | ||
| 5.2.6 Microbubbles | 132 | ||
| 5.3 Theranostics and Imaging | 133 | ||
| 5.3.1 Nuclear Imaging | 133 | ||
| 5.3.2 Computed Tomography | 134 | ||
| 5.3.3 Magnetic Resonance Imaging | 136 | ||
| 5.3.4 Ultrasound | 139 | ||
| 5.3.5 Optical Imaging | 141 | ||
| 5.4 Conclusions | 146 | ||
| References | 147 | ||
| Chapter 6 The Role of Imaging in Nanomedicine Development and Clinical Translation | 151 | ||
| 6.1 Introduction | 151 | ||
| 6.2 Imaging for In vivo Evaluation of the Spatio-temporal Distribution Characteristics of Nanomedicines | 152 | ||
| 6.2.1 Rationale for Spatio-temporal Biodistribution Assessment | 152 | ||
| 6.2.2 Imaging as a Non-invasive Method for Nanoparticle Biodistribution Assessment | 153 | ||
| 6.3 Use of Imaging to Understand and Optimize Nanomedicine Performance | 157 | ||
| 6.3.1 Investigation of Size-dependence and Lesion Targeting Ability | 157 | ||
| 6.3.2 Investigation of the Effectiveness of Active Versus Passive Targeting | 163 | ||
| 6.3.3 Stroma Modification to Enhance Nanomedicine Delivery and Efficacy | 170 | ||
| 6.3.4 Assessment of the Performance of Activatable Nanomedicines | 171 | ||
| 6.4 Clinical Experience and Future Considerations | 175 | ||
| References | 178 | ||
| Chapter 7 Anticancer Agent-Incorporating Polymeric Micelles: from Bench to Bedside | 182 | ||
| 7.1 Introduction | 182 | ||
| 7.2 Anticancer Agents Incorporating Micelles under Clinical Evaluation | 184 | ||
| 7.2.1 NK105, a Paclitaxel-incorporating Micelle | 184 | ||
| 7.2.2 NC-6004, Cisplatin-incorporating Micelle | 187 | ||
| 7.2.3 NC-6300, Epirubicin-incorporating Micelle | 189 | ||
| 7.3 Verification of the EPR Effect using Imaging Mass Spectrometry | 193 | ||
| 7.4 Discussion and Conclusion | 194 | ||
| References | 195 | ||
| Chapter 8 Polymeric Nanoparticles and Cancer: Lessons Learnt from CRLX101 | 199 | ||
| 8.1 Introduction | 199 | ||
| 8.2 Topoisomerase 1 Inhibitors | 200 | ||
| 8.2.1 Carbohydrate-based Polymeric Nanoparticles | 203 | ||
| 8.2.2 Polyamine Polymeric Nanoparticles | 204 | ||
| 8.2.3 HPMA Copolymeric Nanoparticles | 205 | ||
| 8.2.4 PEG Polymeric Nanoparticles | 206 | ||
| 8.2.5 Amphiphilic Polymeric Nanoparticles | 209 | ||
| 8.2.6 Bioconjugates | 210 | ||
| 8.2.7 Non-polymeric Nanoparticles | 211 | ||
| 8.3 Hypoxia Inducible Factor-1 Inhibitors | 211 | ||
| 8.3.1 2ME2 | 211 | ||
| 8.3.2 Camptothecins | 212 | ||
| 8.3.3 siRNA Technologies | 213 | ||
| 8.3.4 Endogenous HIF-1α Inhibitors\r | 213 | ||
| 8.3.5 Other HIF-1α Inhibitors\r | 213 | ||
| 8.4 Cancer Stem Cells | 214 | ||
| 8.5 Combination Therapy | 215 | ||
| 8.6 CRLX101 | 216 | ||
| 8.6.1 CRLX101 Chemistry | 217 | ||
| 8.6.2 CRLX101 Preclinical Results | 217 | ||
| 8.6.3 CRLX101 Clinical Results | 220 | ||
| 8.7 Conclusion | 221 | ||
| References | 224 | ||
| Chapter 9 Nanodelivery Strategies in Breast Cancer Chemotherapy | 233 | ||
| 9.1 Introduction | 233 | ||
| 9.2 Nanocarriers for Drug Delivery to Solid Tumors | 234 | ||
| 9.2.1 Liposomal Nanoparticles | 235 | ||
| 9.3 Doxil®–The First FDA-approved Nano-drug | 236 | ||
| 9.4 Taxane-based Nanodelivery (Abraxane® and Genexol-PM®) | 238 | ||
| 9.5 CrEL-free Formulations of PTX | 240 | ||
| 9.6 Albumin-bound PTX (nab-PTX/Abraxane®) | 240 | ||
| 9.6.1 Clinical Efficacy and Safety of Abraxane® | 242 | ||
| 9.7 Polymeric Paclitaxel Micelles (Genexol-PM®) | 244 | ||
| 9.7.1 Clinical Studies of Genexol-PM® | 246 | ||
| 9.7.2 Clinical Efficacy of Genexol-PM® | 246 | ||
| 9.8 Conclusion | 247 | ||
| References | 248 | ||
| Chapter 10 Developing a Predictable Regulatory Path for Nanomedicines by Accurate and Objective Particle Measurement | 253 | ||
| 10.1 Introduction | 253 | ||
| 10.2 Regulation of Nanomedicines | 254 | ||
| 10.2.1 The Need to Develop Regulatory Pathways for Nanomedicines | 254 | ||
| 10.2.2 Current Status of Nanomedicine Regulation | 256 | ||
| 10.3 Accurate and Objective Particle Measurement | 259 | ||
| 10.3.1 Specific Challenges of Nanoscale Measurements | 260 | ||
| 10.3.2 Important Parameters of Nanoscale Materials Used in Bioapplications | 261 | ||
| 10.4 Current Techniques for Characterising Nanomaterials | 265 | ||
| 10.4.1 Ensemble Measurement Techniques | 267 | ||
| 10.4.2 Single-particle Techniques | 268 | ||
| 10.4.3 TRPS for Accurate Particle-by-particle Measurement | 271 | ||
| 10.5 Conclusions and Outlook | 276 | ||
| References | 276 | ||
| Chapter 11 Nanomedicine: Promises and Challenges | 281 | ||
| 11.1 The Evolution of Nanomedicine | 281 | ||
| 11.2 Unique Capabilities of Nanomaterials: The Promise of Nanomedicine | 282 | ||
| 11.3 Conceptual Issues in Nanomedicine | 283 | ||
| 11.4 Challenges to the Implementation of Nanomedicine | 285 | ||
| 11.5 Conclusion | 286 | ||
| References | 287 | ||
| Chapter 12 The Challenge of Regulating Nanomedicine: Key Issues | 290 | ||
| 12.1 Introduction | 290 | ||
| 12.2 Defining ‘‘Nano\": A Problem for Regulators? | 291 | ||
| 12.3 Lessons Learned from Doxil®: The First FDA-approved Nanodrug | 295 | ||
| 12.4 Baby Steps Lead to Regulatory Uncertainty: The FDA as an Example | 298 | ||
| 12.5 Importance of Understanding Pharmacokinetics and Distribution in Development and Regulatory Submission | 306 | ||
| 12.6 Conclusions | 310 | ||
| References | 312 | ||
| Chapter 13 Doxil® - the First FDA-approved Nano-drug: from Basics via CMC, Cell Culture and Animal Studies to Clinical Use | 315 | ||
| 13.1 Introduction | 315 | ||
| 13.2 Introducing Doxil® | 316 | ||
| 13.3 Doxil®: Historical Perspective in Short | 324 | ||
| 13.4 Clinical Indications for Doxil® | 326 | ||
| 13.5 Doxil®-related Intellectual Property | 327 | ||
| 13.6 From the Failure of DOX-OLV to the Success of Doxil® | 327 | ||
| 13.7 The Obligatory Need for Animal Studies and the Issue of the Relevance of Studies Using Cells in Culture (in vitro) to Doxil® Development | 330 | ||
| 13.7.1 The Issue of Animal Studies | 330 | ||
| 13.7.2 In vitro-In vivo Correlation | 331 | ||
| 13.7.3 Studies Based on Cells in Culture | 332 | ||
| 13.7.4 Lessons Learned from In vitro Cell Culture Studies during Doxil® Development | 333 | ||
| 13.8 The Time is Ripe for Generic Doxil®-like PLDs | 335 | ||
| 13.9 Doxil®: New Findings (2012-2015) | 336 | ||
| 13.10 Doxil® Still Keeps Some Secrets | 341 | ||
| Special Acknowledgements | 341 | ||
| References | 342 | ||
| Subject Index | 346 |