Nanomedicine-Based Approaches for the Treatment of Dementia

Nanomedicine-Based Approaches for the Treatment of Dementia explores a wide range of promising approaches for the diagnosis and treatment of dementia. The book begins with introductory sections on dementia and brain ailments that are followed by further chapters that discuss detailed information about challenges of drug delivery across the blood-brain barrier as well as the current status. This book helps readers design and develop novel drug delivery systems and devices for the treatment of dementia that take advantage of recent advances in nanomedical technologies. Numerous drug delivery systems have been developed recently for dementia. Unfortunately, most of them are ineffective since dementia is not a single disease. It is an umbrella term for several neurodegenerative conditions which alter brain functions. Due to this, there is an urgent need for innovative technologies/nano drug delivery systems to improve the targeting and delivery of therapeutic as well as diagnostic agents specifically for treating dementia. Explores promising approaches for the diagnosis and treatment of dementia Discusses advances in cutting-edge nanomedical technologies Focuses on the design, synthesis and application of nanocarriers in drug delivery Front cover Half title Full title Copyright Dedication Contents Contributors Preface Chapter 1 - Dementia and neurodegenerative disorder: An introduction 1.1 Introduction 1.2 Dementia 1.3 Etiology intended for dementia 1.3.1 Alzheimer’s disease 1.3.2 Cerebrovascular disease 1.3.3 Huntington’s disease 1.3.4 Parkinson’s disease 1.3.5 Creutzfeldt–Jakob disease 1.3.6 Cerebral contusion 1.4 Genetic effects 1.5 Age 1.6 Physical activity 1.7 Comorbidity 1.8 Drugs 1.9 Psychometric symptoms 1.10 Pathophysiology of neurodegenerative disorder; AD 1.10.1 Amyloid beta peptide 1.10.2 Tau proteins 1.10.3 Heat shock protein 1.11 Pathogenesis of Parkinson’s disease 1.12 Pathogenesis of vascular dementia 1.13 Pathogenesis of Huntington’s disease 1.14 Treatment of neurodegenerative disorders 1.14.1 Alzheimer’s disease 1.14.2 Parkinson’s disease 1.14.3 Huntington’s disease 1.14.4 Creutzfeldt–Jakob disease 1.14.5 New drug targets for dementia 1.14.6 Miscellaneous treatment 1.15 Blood–brain barrier 1.16 Structure of blood–brain barrier 1.17 Tight junction involved in BBB 1.18 Features of endothelial and specialized cells forming BBB 1.19 Mechanisms to permeate the blood–brain barrier 1.19.1 Transcellular pathway 1.19.2 Paracellular pathway 1.19.3 Clathrin-mediated endocytosis 1.19.4 Carrier-mediated pathway 1.19.5 Receptor-mediated transport 1.19.6 Blood–brain barrier models 1.19.6.1 In vitro blood–brain barrier models 1.19.6.2 Micro blood–brain barrier models 1.19.6.3 Several advantages of using this model 1.19.6.4 Immortalized rat brain cell lines 1.19.7 In vivo studies 1.19.8 Nanomedicine a therapeutic approach for neurodegenerative disorders and corresponding dementia 1.19.8.1 Nanomedicine for neurodegenerative diseases 1.20 Conclusion Conflict of interest Consent Acknowledgments References Chapter 2 - Dementia: A journey from cause to cure 2.1 Introduction 2.2 Types of dementia 2.3 Alzheimer’s disease 2.4 Etiopathogenesis 2.5 Lewy body dementia 2.6 Etiopathogenesis 2.7 Vascular dementia 2.8 Etiopathogenesis 2.9 Frontotemporal dementia 2.10 Etiopathogenesis 2.11 Current treatments and drugs under clinical investigations 2.12 Conclusion References Chapter 3 - Receptor attacking ligands for active targeting to brain 3.1 Introduction 3.2 Receptor-mediated nanocarrier platforms for brain drug delivery 3.2.1 Insulin receptor 3.2.2 Transferrin receptor 3.2.3 Folate receptor 3.2.4 Lipoprotein receptor 3.2.5 Leptin receptor 3.2.6 Nicotinic-acetylcholine receptors 3.2.7 Scavenger receptor 3.2.8 Interleukin receptors 3.3 Conclusion References Chapter 4 - Dendrimers in the effective management of Alzheimer’s and dementia 4.1 Introduction 4.2 History and definition of dendrimers 4.3 Properties of dendrimers Monodispersity Size and shape Biocompatibility Covalent conjugation strategies Pharmacokinetic properties Self-assembling dendrimers Electrostatic interactions Chemical and physical stability Unimolecular micelles 4.4 Types of dendrimers 4.4.1 PAMAM dendrimers 4.4.2 PPI dendrimers 4.4.3 PLL dendrimers 4.4.4 PPH dendrimers 4.4.5 Carbosilane dendrimers 4.4.6 Other types of dendrimers 4.5 Dendrimer-mediated brain delivery approaches 4.5.1 Bypassing the BBB with invasive approaches 4.5.2 Bypassing the BBB with non-invasive approaches 4.5.3 Traversing the BBB with non-invasive approaches 4.6 Dendrimers in Alzheimer’s disease 4.6.1 Use of PAMAM dendrimers 4.6.2 Use of PPI dendrimer 4.6.3 Use of other dendrimers 4.7 Dendrimers in dementia 4.8 Conclusion References Chapter 5 - Polymeric nanoparticles as drug delivery systems for dementia 5.1 Introduction 5.2 Dementia 5.3 Polymeric nanoparticles 5.3.1 Natural polymers 5.3.2 Synthetic polymers 5.4 Polymeric nanoparticles for treatment and diagnosis of dementia 5.4.1 PLGA 5.4.2 Chitosan 5.4.3 PCL 5.4.4 PBCA 5.5 Functionalization or modification strategies of polymeric nanoparticles for dementia 5.6 Conclusions Acknowledgements References Chapter 6 - Solid lipid nanoparticles-based drug delivery for dementia 6.1 Introduction 6.1.1 Statistics 6.1.2 Definitions, etiology, and pathophysiology 6.1.3 Pharmacotherapy 6.2 Nano-based drug delivery systems in dementia 6.3 Solid lipid nanoparticles as drug delivery systems 6.3.1 Composition of SLN 6.3.2 Methods of SLN preparation 6.3.2.1 High-pressure homogenization method 6.3.2.2 Ultrasonication method 6.3.2.3 Microemulsion method 6.3.2.4 Solvent emulsification–evaporation method 6.3.3 Characterization of SLN 6.3.4 Toxicological aspects of lipid nanoparticles 6.4 Penetration of SLN to the central nervous system 6.4.1 Barriers in the brain 6.4.2 Uptake mechanisms in the brain 6.5 Application SLN in dementia 6.6 Conclusion and final remarks References Chapter 7 - Liposome: A potential drug delivery vector to treat dementia 7.1 Introduction 7.2 Types of dementia 7.2.1 Alzheimer’s disease-associated dementia 7.2.2 Vascular dementia 7.2.3 Lewy body dementia 7.2.4 Frontotemporal dementia 7.2.5 Mixed dementia 7.3 Need of novel drug carrier 7.4 Liposome 7.4.1 Strategies of brain targeting 7.4.1.1 Stealth liposome (PEGylated liposomes) 7.4.1.2 Surface-modified liposome 7.4.1.3 Liposome for direct nose-to-brain drug delivery 7.4.2 In-line research: liposome-based therapies 7.4.2.1 Protein and peptide delivery 7.4.2.2 Gene delivery 7.5 Conclusion Acknowledgment Funding Conflict of Interest References Chapter 8 - Micelles-based drug delivery for dementia 8.1 Introduction 8.2 Interaction of micelles with β-amyloid 8.3 Different routes for micelles delivery in dementia 8.3.1 Oral route 8.3.2 Intranasal route 8.3.3 Intravenous route 8.4 Preparation methods of different micelles 8.4.1 Dialysis method 8.4.2 Direct dissolution method 8.4.3 Solvent evaporation method 8.5 Modified micelles for cellular targeting 8.5.1 Microglial targeting 8.5.2 Mitochondrial targeting 8.5.3 Nucleus targeting 8.6 Therapeutics-loaded micellar systems for different types of dementia 8.6.1 Drug-loaded systems 8.6.2 Genetic material-loaded systems 8.7 Conclusion References Chapter 9 - Biologics for the management of dementia 9.1 Introduction 9.2 Existing treatments 9.3 Biological drug product-based approaches 9.3.1 Monoclonal antibodies 9.3.1.1 Bapineuzumab 9.3.1.2 Solanezumab 9.3.1.3 Gantenerumab 9.3.1.4 Crenezumab 9.3.1.5 Aducanumab 9.3.1.6 Donanemab 9.3.1.7 Canakinumab 9.3.2 Gene therapy 9.3.2.1 Apolipoprotein E 9.3.2.2 Endothelin-converting enzyme 9.3.2.3 Cathepsin B 9.3.2.4 BACE1 proteins 9.3.2.5 Nerve growth factor 9.3.3 Stem cell-based therapeutics 9.3.3.1 Embryonic stem cell 9.3.3.2 Mesenchymal stem cell 9.3.3.3 Neural stem cell 9.3.4 Vaccines 9.4 Biological products-based combination therapy 9.5 Nanotechnology-based biological drug products 9.5.1 Polymeric nanoparticles 9.5.2 Liposomes 9.5.3 Micelles 9.5.4 Inorganic nanoparticles 9.6 Future direction in the management of dementia 9.7 Concluding remark References Chapter 10 - Nanocarriers-based noninvasive approaches for dementia 10.1 Introduction 10.2 Approaches for the treatment of dementia 10.2.1 Molecule-based approaches 10.2.1.1 Medication-based therapies 10.2.1.2 Methods that prevent formation of amyloid-β 10.2.1.2.1 α-secretase activation 10.2.1.2.2 γ-secretase or β-secretase inhibition 10.2.1.3 Methods that promote blocking of Aβ self-assembly 10.2.1.3.1 Modulators based on small molecules 10.2.1.3.2 Immunotherapy 10.2.1.3.3 Modulators based on peptide 10.2.1.3.4 Metal ion-based chelators 10.2.1.3.5 Chaperone proteins 10.2.1.4 Therapies that target tau protein 10.2.1.4.1 Immunotherapy 10.2.1.4.2 Polyphenols 10.2.1.4.3 Peptides that target the core identifying pattern of tau 10.2.2 Noninvasive approaches 10.2.2.1 Light therapy 10.2.2.2 Scanning ultrasound therapy 10.2.2.3 Electric field 10.2.2.4 Brain stimulation (noninvasive) 10.3 Nanocarrier-based invasive approaches 10.4 Nanocarrier-based noninvasive approaches 10.4.1 Nanocarriers approaches for dementia 10.4.2 Nanocarriers approaches for Alzheimer 10.4.3 Nanocarriers approaches for Parkinsonism’s disease 10.5 Clinical trial and future aspects 10.6 Conclusion References Chapter 11 - Futuristic aspect of nanocarriers on targeted delivery for dementia 11.1 Introduction 11.2 Pathophysiology of Alzheimer’s disease 11.2.1 Amyloid-Beta (Aβ) and amyloid hypothesis 11.2.2 Tau protein 11.2.3 Link between Aβ and tau 11.3 Protein degradation in Alzheimer’s disease 11.3.1 Ubiquitination 11.3.1.1 Ubiquitin activation 11.3.1.2 Transfer of ubiquitin to an E2 enzyme 11.3.1.3 Ubiquitylation of target proteins 11.4 Conventional treatment approached and their limitation 11.5 Traditional drug delivery technologies confront difficulties in targeting exact parts of the brain to treat the neuro ... 11.5.1 Blood–brain barrier (BBB) 11.5.2 Efflux transporters 11.5.3 Blood cerebrospinal fluid barrier 11.5.4 Tight junctions (TJs) 11.6 Novel drug delivery strategies for targeting brain to treat neurodegenerative disorders 11.6.1 Liposomes 11.6.2 Dendrimers 11.6.3 Antibody-coated nanoparticles 11.6.4 Polymeric micelles 11.6.5 Polymeric nanoparticles 11.6.6 Gold nanoparticles 11.6.7 Quantum dot 11.6.8 Carbon nanotubes 11.6.9 Viral carrier 11.6.10 Nanocrystals 11.6.11 Microneedles 11.7 Novel proteolytic therapies for Alzheimer’s disease 11.7.1 Small-molecule PROTACs peptide 11.7.2 TH006 11.7.2.1 TH006 can induce tau degradation 11.7.2.2 TH006 can increase polyubiquitination of tau depending on VHL E3 ligase 11.7.3 The role of neprilysin-2 (NEP-2) in amyloid-beta clearance 11.8 Conclusion and prospects for the future References Index Back cover