Targeted Drug Delivery

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