Systemic Delivery Technologies in Anti-Aging Medicine: Methods and Applications

Preface
Contents
Contributors
Part IFundamentals and Experimental Techniques in Systemic Delivery
1 Systemic Delivery in Anti-aging Medicine: An Overview
	1.1 Introduction
		1.1.1 A Three-Level Strategy for Anti-Aging Approaches
	1.2 Translation of Basic Research: From Bench to Clinic
		1.2.1 Basic Genetic/Genomic Research
		1.2.2 Mechanistic Research on Genetic/Genomic Manipulation
	1.3 Importance of Systemic Delivery to Anti-Aging Medicine
		1.3.1 Viral Nanoparticles
		1.3.2 Inorganic Carriers
		1.3.3 Organic Carriers
		1.3.4 Hybrid Nanocarriers
		1.3.5 Xenobot, a “Futuristic” Drug Delivery System
	1.4 Clinical Trials
	1.5 Summary and Outlooks
	References
2 Current Status of Systemic Drug Delivery Research: A Bibliometric Study
	2.1 Introduction
	2.2 Methodology
	2.3 Analysis Results
		2.3.1 Analysis of Publication Years
		2.3.2 Analysis of Citations
		2.3.3 Analysis of Countries
		2.3.4 Analysis of Topics
		2.3.5 Analysis of Keywords
	2.4 Summary and Outlooks
	References
3 Characterization Techniques for Studying the Properties of Nanocarriers for Systemic Delivery
	3.1 Introduction
	3.2 Shape and Size Distribution
		3.2.1 Transmission Electron Microscopy
		3.2.2 Scanning Electron Microscopy
		3.2.3 Cryo-TEM
		3.2.4 Atomic Force Microscopy
		3.2.5 X-ray Diffraction
		3.2.6 Small Angle X-ray Scattering
		3.2.7 Dynamic Light Scattering
		3.2.8 Tuneable Resistive Pulse Sensing (TRPS)
		3.2.9 Nanoparticle Tracking Analysis
	3.3 Surface Charge
		3.3.1 Laser Doppler Anemometry
		3.3.2 Single Particle Electrokinetic Measurements
	3.4 Porosity
	3.5 Viscosity
	3.6 Summary and Outlooks
	References
4 In Vivo Assessment of the Efficiency of Systemic Delivery
	4.1 Introduction
	4.2 In Vivo Assessment Models
		4.2.1 Selection of Animal Models
		4.2.2 Zebrafish as an Emerging Model for In Vivo Assessment
		4.2.3 Animal Models and In Vivo Research Techniques
	4.3 In Vivo Assessment of Systemic Delivery
		4.3.1 Based on the Route of Administration
		4.3.2 Based on the Specialty of the Molecule Delivered
		4.3.3 Based on the Dosage Form
	4.4 Summary and Outlooks
	References
Part IISystemic Delivery Techniques Based on Prodrug Design and Synthetic Materials
5 Prodrug Design to Enhance Bioavailability and Systemic Delivery
	5.1 Introduction
	5.2 General Design Principles of a Prodrug
	5.3 Designing Prodrugs for Increasing Oral Bioavailability
	5.4 Prolonged Duration of Action
	5.5 Decreasing Toxicity of Drugs/Bioactive Compounds
	5.6 Targeting Drugs to Specific Tissues/Organs
	5.7 Summary and Outlooks
	References
6 Development of Biodegradable Polymeric Nanoparticles for Systemic Delivery
	6.1 Introduction
	6.2 Advantages of Biodegradable Polymeric Nanoparticles in Biomedical Use
	6.3 Use of Lactide and Glycolide Polymers in Drug Delivery
	6.4 Nanoparticle Fabrication from Lactide/Glycolide Polymers
		6.4.1 Phase Separation of Polymer
		6.4.2 Solvent Evaporation and Extraction Methods
		6.4.3 Spray Drying Method
		6.4.4 Formation of Microparticles Using Supercritical Fluids
	6.5 Potential of Polyanhydride in Systemic Delivery
	6.6 Parameters for the Design of Polymeric Particulate Systems
		6.6.1 Particle Size
		6.6.2 Surface Charge
		6.6.3 Hydrophilicity/Hydrophobicity
		6.6.4 In Vitro and In Vivo Study
	6.7 Summary and Outlooks
	References
7 Use of Nanoparticulate Systems for Tackling Neurological Aging
	7.1 Introduction
	7.2 Nanosystems for Neurological Drug Delivery
		7.2.1 Nanoliposomes
		7.2.2 Nanogels
		7.2.3 Carbon Nanotubes (CNTs)
		7.2.4 Nanoemulsions
	7.3 Dendrimers
	7.4 Polymeric Nanoparticles for Neurological Drug Delivery
		7.4.1 Natural Polymers
		7.4.2 Synthetic Polymers
	7.5 Clinical Considerations and Regulatory Requirements
	7.6 Other Challenges and Considerations for the Regulatory Requirement
	7.7 Summary and Outlooks
	References
Part IIISystemic Delivery Techniques Based on Biological Materials
8 Lipid-Based Nano-delivery of Phytobioactive Compounds in Anti-aging Medicine
	8.1 Introduction
	8.2 Main Types of Lipid-Based Nano-delivery Systems and Possible Applications
		8.2.1 Nanoemulsions
		8.2.2 Self-emulsifying Drug Delivery Systems
		8.2.3 Solid Lipid NPs
		8.2.4 Nanostructured Lipid Carriers
	8.3 Nanoformulations of Anti-aging Drugs
		8.3.1 Nano-curcumin
		8.3.2 Nano-auercetin
		8.3.3 Nano-resveratrol
		8.3.4 Nano-genistein
		8.3.5 Nano-epigallocatechin-3-Gallate
		8.3.6 Other Phytocompound-Based Lipid Nanocomposites
	8.4 Summary and Outlooks
	References
9 Albumin-Based Carriers for Systemic Delivery to Tackle Cancer
	9.1 Introduction
	9.2 Overview of Albumin
		9.2.1 Human Serum Albumin (HSA)
		9.2.2 Bovine Serum Albumin (BSA)
		9.2.3 Egg White Albumin (Ovalbumin)
	9.3 Albumin as a Drug Carrier
		9.3.1 Albumin as Carrier of Platinum Drugs
		9.3.2 Albumin as Carrier of Curcumin
		9.3.3 Albumin as Carrier of Doxorubicin
		9.3.4 Albumin as Carrier of Paclitaxel
		9.3.5 Albumin as Carrier of Methotrexate
		9.3.6 Albumin as Carrier of 5-Fluorouracil
	9.4 Albumin as Coating Agent
	9.5 Summary and Outlooks
	References
10 Exosomes as Vehicles for Systemic Drug Delivery
	10.1 Introduction
	10.2 Exosome Biogenesis
	10.3 Exosome Recognition
	10.4 Exosome Uptake
	10.5 Exosome Composition and Functions
	10.6 Exosome Isolation
	10.7 Exosome Sourcing
	10.8 Drug Loading Methods
		10.8.1 Pre-loading Methods
		10.8.2 Post-loading Methods
	10.9 Exosome Delivery
	10.10 Use of Exosome in Disease Treatment
	10.11 Summary and Outlook
	References
Part IVSystemic Delivery Techniques Based on Physical Means
11 Use of Physical Approaches for Systemic Drug Delivery
	11.1 Introduction
	11.2 Methods and Applications
		11.2.1 Ultrasound-Based Method
		11.2.2 Electrical-Based Method
		11.2.3 Magnetic Based Delivery Method
		11.2.4 Photo-Based Method
		11.2.5 Microneedles
		11.2.6 Other Permeation Enhancer Based Systems
	11.3 Summary and Outlooks
	References
12 Inhalation as a Means of Systemic Drug Delivery
	12.1 Introduction
	12.2 Rationale for Delivery of Systemic Drugs via the Respiratory System
	12.3 Inhalation Aerosol as a Drug Carrier
	12.4 The Significance of Drug Formulation
	12.5 The Significance of an Inhalation System
	12.6 Current and Future Concepts of Systemic Drug Delivery via Inhalation
	12.7 Summary and Outlooks
	References
Part VModification of Carrier Properties for Systemic Delivery
13 Use of Electrospinning to Enhance the Versatility of Drug Delivery
	13.1 Introduction
	13.2 Methodology for Coupling Between Experiments and Numerical Modeling
	13.3 Results of Experimental and Numerical Modeling
	13.4 Summary and Outlooks
	References
14 Surface Modification Strategies in Enhancing Systemic Delivery Performance
	14.1 Introduction
	14.2 Rationale of Using Particulate System and Concept of Biorecognition
		14.2.1 The Mononuclear Phagocyte System
		14.2.2 Adsorption of Proteins to Surfaces
		14.2.3 Phagocytosis (Opsonization) as a Surface Phenomenon
		14.2.4 Biopharmaceutical Factors Affecting the Uptake of Particulate Systems
	14.3 Surface Modification or Steric Protection with Polymers
		14.3.1 Polyethylene Glycol (PEG)
		14.3.2 Block Copolymers of Ethylene Oxide and/or Propylene Oxide
	14.4 Surface-Modified Particulates in Sequestering Multidrug Resistance Proteins
	14.5 Surface Modification as a Strategy to Target Non-MPS Organs
	14.6 Summary and Outlooks
	References
15 Layer-by-Layer Functionalization for Oral Liposomal Formulations in Anti-aging Medicine
	15.1 Introduction
	15.2 Preparation of LbL-Functionalized Liposomes
	15.3 Principles of Molecular Design of LbL-Functionalized Liposomes
	15.4 Engineering LbL Coatings to Enhance Intestinal Absorption
	15.5 Summary and Outlook
	References
16 Use of Cell-Penetrating Peptides to Enhance Delivery Performance
	16.1 Introduction
	16.2 Experimental Section
		16.2.1 Ethical Approval
		16.2.2 Recombinant Proteins
		16.2.3 Otocystic Inoculation of Recombinant Proteins into Mouse Embryos
		16.2.4 Treatment Via the Round Window Membrane in Adult Guinea Pigs
		16.2.5 Noise Exposure
		16.2.6 Auditory Thresholds
	16.3 Results and Discussion
		16.3.1 Protein Transduction into Embryonic Inner Ear in Mus musculus
		16.3.2 Protein Transduction into Adult Inner Ear in Guinea Pigs
	16.4 Summary and Outlooks
	References
Part VIOptimization of Delivery Technologies for Intervention Development
17 Use of Numerical Simulation in Carrier Characterization and Optimization
	17.1 Introduction
	17.2 Experimental and Numerical Modeling
	17.3 Results of Experimental and Numerical Modeling
	17.4 Summary and Outlooks
	References
18 Parameters and Strategies to Overcome Barriers to Systemic Delivery
	18.1 Introduction
	18.2 Factors that Affect the Developability of Drug Candidates
		18.2.1 Solubility
		18.2.2 Permeability
		18.2.3 Drug Stability
		18.2.4 Metabolic Instability
	18.3 Barriers to Systemic Drug Delivery
		18.3.1 Physiological Barriers
		18.3.2 Biochemical Barriers
		18.3.3 Chemical Barrier
	18.4 pH Responsive Carriers as a Solution to Oral Drug Delivery Challenges
	18.5 Barriers to Tumor Drug Delivery
		18.5.1 Heterogenous Tumor Vasculature
		18.5.2 Hypoxia and Acidic Regions in Tumor
		18.5.3 Interstitial Fluid Pressure
	18.6 Challenges with Nanotechnology Approach in Tumor Delivery
		18.6.1 Renal Clearance
		18.6.2 The Concept of “The Enhanced Permeation and Retention Effect” and Its Role in Nanoparticle-Based Drug Delivery
		18.6.3 Extra-Cellular Matrix (ECM) of Tumor
		18.6.4 Matrix Metalloproteinases
	18.7 Challenges Specific to Brain Drug Delivery by Nanotechnology
	18.8 Nanotechnology as a Solution to Brain Delivery via BBB
	18.9 Summary and Outlooks
	References
19 Blood Interactions with Nanoparticles During Systemic Delivery
	19.1 Introduction
	19.2 Roles of Nanoparticulate Systems in Systemic Delivery
	19.3 Manipulation of Pharmacokinetics and Biodistribution
	19.4 Enhancement of Hematocompatibility for Systemic Delivery
	19.5 Other Factors to be Considered for Intervention Execution
	19.6 Summary and Outlooks
	References
20 New Directions for Use of Systemic Drug Delivery in Anti-aging Medicine
	20.1 Anti-aging Medicine: A Basic Overview
	20.2 Endothelium (Re)programming as a New Concept for Anti-aging Medicine
	20.3 Early Measures and Recommendations for Modulating Aging
	20.4 Fecal Microbiota Transplantation for Modulating Microbiota
	20.5 Cellular Reprogramming for Tissue Regeneration
	20.6 Summary and Outlooks
	References