Targeted Drug Delivery

✍ Scribed by Bachhav Y. (ed.)

• Publisher: Wiley-VCH
• Year: 2023
• Tongue: English
• Leaves: 449
• Series: Methods and Principles inMedicinal Chemistry
• Category: Library

✦ Synopsis

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.

✦ Table of Contents

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