Targeted Drug Delivery

Description

Novel approaches in targeted drug delivery for both small molecule and biopharmaceutical drugs Targeted Drug Delivery explores a new frontier in drug research that has become a focus for developing novel medications. The work discusses a wide range of approaches for targeting small molecules as well as peptide and macromolecular drugs, from prodrugs to drug conjugates to drug carriers and devices, helping readers to stay up to date on the latest developments in the field. The following key topics are addressed: Antibody conjugates, prodrugs, and suicide gene therapeuticsProtac technology for selectively degrading target proteinsDelivery of nucleic acid drugsNovel drug carriers, such as liposomes, vesicles, and nanoparticlesUnmet medical needs for which there is a large market potential, such as viral infections and cancer For chemists, pharmacologists, and professionals in the wider pharmaceutical industry, Targeted Drug Delivery is a comprehensive guide on how to solve the greatest challenge in treating many diseases: delivering a pharmaceutically active substance to the target tissue in the body. Cover Half Title Methods and Principles inMedicinal Chemistry Series: Volume 82 Targeted Drug Delivery Copyright Contents A Personal Foreword Preface 1. Basics of Targeted Drug Delivery 1.1 Introduction 1.1.1 Concept of Bioavailability and Therapeutic Index 1.2 Targeted Drug Delivery 1.3 Strategies for Drug Targeting 1.3.1 Passive Targeting 1.3.2 Active Targeting 1.3.3 Physical Targeting 1.4 Therapeutic Applications of Targeted Drug Delivery 1.4.1 Diabetes Management 1.4.2 Neurological Diseases 1.4.3 Cardiovascular Diseases 1.4.4 Respiratory Diseases 1.4.5 Cancer Indications 1.5 Targeted Dug-Delivery Products 1.6 Challenges 1.6.1 Passive Targeting and EPR Effect 1.6.2 Active Targeting 1.7 Scale-up and Challenges 1.8 Current Status 1.9 Conclusion and Prospects References 2. Addressing Unmet Medical Needs Using Targeted Drug-Delivery Systems: Emphasis on Nanomedicine-Based Applications 2.1 Introduction 2.2 Targeted Drug-Delivery Systems for Unmet Medical Needs 2.2.1 Targeting Ligands 2.2.2 Targeting Approaches 2.3 Regulatory Aspects and Clinical Perspectives 2.4 Conclusion and Future Outlook List of Abbreviations References 3. Nanocarriers-Based Targeted Drug Delivery Systems: Small and Macromolecules 3.1 Nanocarriers (Nanomedicine) – Overview and Role in Targeted Drug Delivery 3.2 Passive Targeting Approaches 3.2.1 Enhanced Permeability and Retention-Effect-Based Targeting 3.3 Active Targeting Approaches 3.4 Stimuli Responsive Targeted NCs 3.4.1 Redox Stimuli Responsive Targeted NCs 3.4.2 pH Stimuli Responsive Targeted NCs 3.4.3 Enzyme Stimuli Responsive Targeted NCs 3.4.4 Temperature Stimuli Responsive Targeted NCs 3.4.5 Ultrasound Stimuli Responsive Targeted NCs 3.4.6 Magnetic Field Stimuli Responsive Targeted NCs 3.5 Conclusion and Future Prospects References 4. Liposomes as Targeted Drug-Delivery Systems 4.1 Introduction 4.2 Liposome Commercial Landscape 4.3.1 Selection of Lipids 4.3 Important Considerations in Development and Characterization of Liposomes 4.3.2 Drug : Lipid Ratio 4.3.3 PEGylation 4.3.4 Ligand Anchoring 4.3.5 Drug-Loading Techniques 4.3.6 Physicochemical Characterization 4.3.7 Manufacturing Process 4.3.8 Product Stability 4.4 Targeted Delivery of Liposomes 4.4.1 Passive Targeting 4.4.2 Active-Targeted Delivery 4.5 Recent Clinical Trials with Liposomes with Investigational Liposome Candidates 4.6 Factors Influencing the Clinical Translation of Liposomes for Targeted Delivery 4.7 Conclusions and Future of Prospects of Targeted Liposomal-Delivery List of Abbreviations 5. Antibody–Drug Conjugates: Development and Applications 5.1 Introduction 5.2 Design of ADCs 5.2.1 Antibody 5.2.2 Linker 5.2.3 Payload 5.3 Mechanism of Action 5.4 Pharmacokinetic Considerations for ADCs 5.4.1 Heterogeneity of ADCs 5.4.2 Bioanalytical Considerations for ADCs 5.4.3 Pharmacokinetic Parameters of ADCs 5.5 Applications of ADCs 5.5.1 Approved ADCs in the Market 5.5.2 Use of ADCs in Rheumatoid Arthritis 5.5.3 Use of ADCs in Bacterial Infections 5.5.4 Use of ADCs in Ophthalmology 5.6 Resistance of ADC 5.7 Regulatory Aspects for ADCs 5.7.1 Role of ONDQA 5.7.2 Role of OBP 5.8 Conclusion and Future Direction References 6. Gene-Directed Enzyme–Prodrug Therapy (GDEPT) as a Suicide Gene Therapy Modality for Cancer Treatment 6.1 Introduction 6.2 GDEPT for Difficult-to-Treat Cancers 6.2.1 High-Grade Gliomas (HGGs) 6.2.2 Triple-Negative Breast Cancer (TNBC) 6.2.3 Other Cancers 6.3 Novel Enzymes for GDEPT 6.4 Conclusions References 7. Targeted Prodrugs in Oral Drug Delivery 7.1 Introduction 7.1.1 Classic vs. Modern Prodrug Approach 7.2 Modern, Targeted Prodrug Approach 7.2.1 Prodrug Approach-Targeting Enzymes 7.2.2 Prodrug Approach Targeting Transporters 7.3 Computational Approaches in Targeted Prodrug Design 7.4 Discussion 7.5 Future Prospects and Clinical Applications 7.6 Conclusion References 8. Exosomes for Drug Delivery Applications in Cancer and Cardiac Indications 8.1 Extracellular Vesicles: An Overview 8.1.1 Evolution of Exosomes 8.1.2 Exosomes as Delivery Vehicles for Therapeutics 8.2 Exosomes as Cancer Therapeutics 8.2.1 Influence of Donor Cells 8.2.2 Different Therapeutic Cargo Explored in Cancer Therapy 8.3 Exosome Based Drug Delivery for Cardiovascular Diseases 8.3.1 Delivery of Cardioprotective RNAs 8.3.2 Exosomes Modified with Cardiac Targeting Peptides 8.4 Clinical Evaluations and Future Aspects 8.5 Conclusion References 9. Delivery of Nucleic Acids, Such as siRNA and mRNA, Using Complex Formulations 9.1 Introduction 9.2 NA-Based Complex Delivery System 9.2.1 Classical NA-Based Complex Delivery System 9.2.2 Advanced NA-Based Complex Delivery Systems 9.3 Applications of NA-Complex Delivery Systems 9.3.1 Genome Editing 9.3.2 Cancer Therapy 9.3.3 Protein Therapy 9.4 Future Prospective 9.5 Conclusion References 10. Application of PROTAC Technology in Drug Development 10.1 Introduction 10.2 Design of PROTACS: A Brief Overview 10.3 Therapeutic Applications of PROTACs 10.3.1 Cancer 10.3.2 Neurodegenerative Disorders 10.3.3 Immunological Diseases 10.3.4 Viral Infections 10.4 Challenges and Limitations in the Development PROTACs 10.5 Future Perspectives References 11. Metal Complexes as the Means or the End of Targeted Delivery for Unmet Needs 11.1 Introduction 11.2 Class 1: Chaperones 11.2.1 Chaperones that Protect Drugs 11.2.2 Delivery to the Cells or Environments to Be Targeted 11.2.3 Release from the Metal Where and When Required 11.3 Class 2: Active Metal Complexes 11.3.1 Targeted Platinum Agents 11.4 Class 3: Dual-Threat Metal Complexes 11.5 Targeting Strategies: The Chemical and Physical Environment 11.5.1 Hypoxia 11.5.2 pH-Based Targeting 11.5.3 The EPR Effect 11.6 Targeting Strategies: Transporters 11.7 Targeting Strategies: Enzyme Activation 11.8 Other Targeting Strategies 11.9 Conclusions References 12. Formulation of Peptides for Targeted Delivery 12.1 Introduction 12.2 Peptides Used in Cancer Therapy 12.2.1 Lung Cancer 12.2.2 Melanoma 12.2.3 Pancreatic Cancer 12.2.4 Brain Cancer 12.2.5 Breast Cancer 12.2.6 Leukemia 12.3 Peptide-Targeting Based on Site of Action 12.3.1 Topical Delivery of Peptides 12.3.2 Ocular Delivery of Peptides 12.3.3 Brain Delivery of Peptides 12.3.4 Lung-Targeted Delivery of Peptides 12.4 Conclusion and Future Prospects References 13. Antibody-Based Targeted T-Cell Therapies 13.1 Introduction 13.2 Immune-Directed Cancer Cell Death 13.3 Immunotherapy Strategies in Cancer 13.4 T-Cell Therapy 13.5 Naturally Occurring T Cells 13.6 Genetically Modified Occurring T Cells 13.7 Clinical Implication of T-Cell and CAR-T-Cell Therapy: 13.8 Antibody-Induced T-Cell Therapy 13.9 A Bispecific Antibody (BsAbs)-Induced T-Cell Therapy 13.10 Formats of BsAbs 13.11 Triomab Antibodies in T-Cell Therapy 13.12 Bispecific Antibodies in T-Cell Therapy 13.13 Clinically Approved T-Cell-Activating Antibodies 13.14 Prospects 13.15 Conclusion References 14. Devices for Active Targeted Delivery: A Way to Control the Rate and Extent of Drug Administration 14.1 Introduction 14.2 Macrofabricated Devices – Drug Infusion Pumps 14.2.1 Peristaltic Pumps 14.2.2 Gas-Driven Pumps 14.2.3 Osmotic Pumps 14.2.4 Insulin Pumps 14.3 Microfabricated and Nanofabricated Drug Delivery Devices 14.3.1 Microelectromechanical Systems (MEMS) 14.3.2 Nanofabricated Drug Delivery Devices 14.4 Noninvasive Active Drug Delivery Systems: Iontophoresis 14.5 Conclusions Acknowledgments List of Abbreviations References 15. Drug Delivery to the Brain: Targeting Technologies to Deliver Therapeutics to Brain Lesions 15.1 Introduction 15.2 Brain Tumor 15.2.1 Obstacles to Brain Tumor-Targeted Delivery 15.2.2 Brain-Tumor-Focused Nano-Drug Delivery 15.3 Neurodegenerative Diseases 15.3.1 Alzheimer’s Disease (AD) 15.3.2 Parkinson’s Disease 15.3.3 Cerebrovascular Disease 15.3.4 Inflammatory Diseases (ID) 15.3.5 Drug Delivery for Multiple Sclerosis (MS) 15.4 Drug Delivery for CNS Disorders 15.4.1 Tau Therapy 15.4.2 Immunotherapy 15.4.3 Gene Immunotherapy (GIT) 15.4.4 Chemotherapy (CT) 15.4.5 Photoimmunotherapy (PIT) 15.5 Future Prospects 15.6 Conclusions List of Abbreviations References Index