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