Nano Medicine and Nano Safety: Recent Trends and Clinical Evidences

Preface
Contents
Contributors
Part I: Applications of Nano Biotechnology in the Development of Nano Medicine
	1: Nanobiotechnology and Its Application in Nanomedicine: An Overview
		1.1 Introduction
			1.1.1 Advantages of Nanomedicine
		1.2 Application of Nanobiotechnology in Nano Medicine
			1.2.1 Diagnosis
				1.2.1.1 Nanobiosensors
				1.2.1.2 Biochips/Microarray
				1.2.1.3 Nanopore Technology
				1.2.1.4 Biobarcode
				1.2.1.5 Nanoparticle Based Imaging and Labeling
				1.2.1.6 Nanoproteomic Based Diagnosis
			1.2.2 Therapeutics
				1.2.2.1 Polymeric Nanoformulation
				1.2.2.2 Liposomes
				1.2.2.3 Nanogels
				1.2.2.4 siRNA
				1.2.2.5 Dendrimers
				1.2.2.6 Gene Drug Delivery
				1.2.2.7 Other Nanoformulations
				1.2.2.8 Nano Surgery
				1.2.2.9 Medical Implants
			1.2.3 Clinical Advances and Patents
		1.3 Challenges for Nanobiotechnology in Nanomedicine
		1.4 Conclusion and Future Aspects
		References
	2: Nanobiotechnology for Therapeutic Targeting of Circulating Tumor Cells in the Blood
		2.1 Introduction
		2.2 Biology of Circulating Tumor Cells
			2.2.1 Survival of CTCs in Blood Circulation
			2.2.2 Entry of CTCs in the Bloodstream
			2.2.3 CTC Single Cell Vs. CTC Clusters
			2.2.4 Epithelial Plasticity of CTCs
			2.2.5 CTC Response to Reactive Oxygen Species (ROS)
			2.2.6 CTC Interaction with Platelets
			2.2.7 CTC Interactions with Immune Cells
		2.3 Advanced Nanobiotechnology for Therapeutic Targeting of CTCs
			2.3.1 Effect of Nanoparticle Morphology on Their Fate in Blood Circulation
			2.3.2 RBC-Based Nanoplatform for CTC Targeting
			2.3.3 Neutrophil-Based Nanoplatform for CTC Targeting
			2.3.4 Targeting CTCs with Platelet Membrane-Functionalized Particles
			2.3.5 Liposomes
			2.3.6 DNA-Based Nanodevices
			2.3.7 Dendrimers
			2.3.8 Mesoporous Silica Nanoparticles (MSN)
			2.3.9 Polymeric Micelles
		2.4 Conclusion
		References
	3: Application of Nanobiotechnology in Clinical Diagnosis
		3.1 Introduction
			3.1.1 Classification of Nanoparticles
			3.1.2 Properties of Quantum Dots
				3.1.2.1 Enhancement of Band Gap
				3.1.2.2 Blue Shift
				3.1.2.3 Large Surface to Volume Ratio
				3.1.2.4 Intense Photoluminescence
			3.1.3 Nanobiosensors
				3.1.3.1 Bimolecular Transduction
				3.1.3.2 Label-Based Detection
				3.1.3.3 Label-Free Detection Methods
					Electrical Detection
					Optical Detection
		3.2 Medical Applications of Nanostructures
			3.2.1 Nanostructured Surfaces
			3.2.2 Nanoscale for Molecular Identification
			3.2.3 Gold Nanoparticles for Diagnostics
			3.2.4 Quantum Dot towards Application in Cancer Cell
			3.2.5 Nanotechnology-Based Biochips
			3.2.6 Infectious Diseases with Nanodiagnostics
			3.2.7 Nanoparticle Hyperthermia as Clinical Cancer Therapy
		3.3 The Next Prospects
		3.4 Challenges with the Use of Nanostructures
		3.5 Conclusion
		References
	4: Anti-diabetic Nano-formulation from Herbal Source
		4.1 Introduction
		4.2 Anti-diabetic Drugs from Herbal Sources
			4.2.1 Anti-diabetic Herbal Sources Indigenous to India and Special Emphasis on Northeast India
			4.2.2 Anti-diabetic Herbal Sources from Rest of the World
		4.3 Some Prominent Isolated Compounds Extracted from Herbal Sources with Their Pharmacological Targets for Mitigating Diabetes
			4.3.1 Regulation of Insulin Secretion By Herbal Drugs
				4.3.1.1 Dandelion (Taraxacum officinale)
				4.3.1.2 Vitis vinifera L
				4.3.1.3 Cuminaldehyde, Cuminol and Cuminol
				4.3.1.4 Resveratrol
				4.3.1.5 Berberine
				4.3.1.6 Gymnemic Acid
			4.3.2 Antioxidant Perspectives of Herbal Drugs in Oxidative Stress
				4.3.2.1 Swertiamarin
				4.3.2.2 Corn Silk (Zea mays L.)
				4.3.2.3 Silybin
			4.3.3 Herbal Drugs-Assisted Alleviation of Peripheral Insulin Resistance
				4.3.3.1 Botanical Mixture of American Ginseng, Fenugreek Seed, Mulberry Leaf Extracts
				4.3.3.2 Emodin
			4.3.4 Inhibition of Glucose Absorption By Herbal Drugs
				4.3.4.1 Nigella Sativa
				4.3.4.2 Feruloylated Arabinoxylan Mono- and Oligosaccharides (FAXmo)
				4.3.4.3 Tomatoside A
				4.3.4.4 Stevioside
				4.3.4.5 Quercetin
				4.3.4.6 Myricitrin
			4.3.5 Diverse Pharmacological Role of Herbal Drugs in Alleviating Diabetes Mellitus
				4.3.5.1 Compound K
				4.3.5.2 Mediterranean Diet
				4.3.5.3 Vitamin D
				4.3.5.4 Curcumin
				4.3.5.5 Capsicum Oleoresin
				4.3.5.6 Naringenin
				4.3.5.7 Baicalin
				4.3.5.8 Scutellarin
		4.4 Application of Nanotechnology for Anti-diabetic Herbal Formulation
			4.4.1 Material-Based Nanoformulation
				4.4.1.1 Nano-carriers
				4.4.1.2 Polymeric Nanoparticles
				4.4.1.3 Solid Lipid Nanoparticles
				4.4.1.4 Liposomes
				4.4.1.5 Microemulsion and Nanoemulsion
		4.5 Challenges in Developing Herbal-Based Nanoformulation
		4.6 Conclusion
		References
	5: Nanomaterials for Alternative Antibiotic Therapy
		5.1 Introduction
		5.2 Nanoparticles as Antimicrobials
			5.2.1 Inorganic Nanoparticles
			5.2.2 Organic Nanoparticles
			5.2.3 Antibacterial Properties and Mechanism of Action of Nanoparticles
			5.2.4 Recent Studies on Nanoparticles Against Microorganism
		5.3 Conclusion
		References
Part II: Nano Medicine: Concept, Development, Clinical Applications and Evidences
	6: Nanomedicines and Nanodrug Delivery Systems: Trends and Perspectives
		6.1 Introduction
		6.2 Types of Nanoparticles with Potential Benefit to Targeted Drug Delivery
		6.3 Nanomedicines for Improvement of Drug Delivery
			6.3.1 Anticancer Nanomedicines
			6.3.2 Antiretroviral Nanomedicines
			6.3.3 Antidiabetic Nanomedicines
			6.3.4 Antimalarial Nanomedicines
			6.3.5 Anti-Inflammatory Nanomedicines
			6.3.6 Antimicrobial Nanomedicines
			6.3.7 Nanomedicines for Neurodegenerative Diseases
			6.3.8 Nanomedicines for Gene Therapy
		6.4 Recent Patents Issued in the Area of Nanomedicine Research
		6.5 Clinical Evidence of Nanomedicines (Marketed Nanoformulations)
		6.6 Promises and Challenges of Nanomedicines for Drug Delivery
		6.7 Conclusion and Future Perspectives
		References
	7: Nanomedicines in Drug Delivery from Synthetic and Natural Sources to Their Clinical Applications
		7.1 Introduction
		7.2 Synthetic Biopolymer-Based Nanomedicines and Drug Delivery
		7.3 Natural Biopolymer-Based Nanomedicine and Drug Delivery
		7.4 Natural Product-Based Nanomedicine and Drug Delivery
		7.5 Clinical Application of Nanomedicines
		7.6 Conclusion and Future Perspectives
		References
	8: Transdermal Nanomedicines for Reduction of Dose and Site-Specific Drug Delivery
		8.1 Introduction
			8.1.1 Transdermal Drug Delivery
			8.1.2 Skin Physiology
				8.1.2.1 Structure of the Skin
				8.1.2.2 Epidermis
				8.1.2.3 Dermis
				8.1.2.4 Hypodermis
				8.1.2.5 Reservoir Capacity of Skin
				8.1.2.6 Metabolic Activity of Skin
		8.2 Mechanism of Skin Permeation
			8.2.1 Skin Pharmacokinetics
				8.2.1.1 Mechanism of Rate-Controlled Transdermal Drug Delivery
			8.2.2 Dose Reduction Through TDDS
		8.3 Nanomedicine
			8.3.1 Therapeutic Purpose of Nanomedicine
		8.4 Nanomedicine in TDDS
			8.4.1 Transethosomes
			8.4.2 Nanoethosomes
			8.4.3 Aspasomes
		8.5 Different Formulations of Transdermal Drug Delivery
			8.5.1 Advancement of TDDS
			8.5.2 Passive Delivery of Protein Drugs
			8.5.3 Iontophoresis
			8.5.4 Electroporation
			8.5.5 Cavitational Ultrasound
			8.5.6 Microneedles
			8.5.7 Thermal Ablation
			8.5.8 Carrier Supportive Adjuvants
			8.5.9 Peptide Chain-Mediated Delivery
				8.5.9.1 Cell-Penetrating Peptides
				8.5.9.2 Skin-Penetrating Peptides
			8.5.10 Antimicrobial Peptide Magainin
			8.5.11 Different Formulations in Transdermal Nanomedicine
		8.6 Drug Targeting and its Importance
		8.7 Nanoformulation-Mediated Site-Specific Delivery of Drug Through Transdermal Drug Delivery
			8.7.1 Physical Techniques
		8.8 Nonphysical Techniques
			8.8.1 Site-Specific Delivery of Drug for Cutaneous Disorder
				8.8.1.1 Melanoma
				8.8.1.2 Psoriasis
				8.8.1.3 Alopecia
				8.8.1.4 Wound Healing
			8.8.2 Treatment of Non-Cutaneous Disorders
				8.8.2.1 Rheumatoid Arthritis
				8.8.2.2 Parkinson
				8.8.2.3 Diabetes Mellitus
			8.8.3 Advanced Cell Targeting by CPPs (Cell Penetrating Peptides)
		8.9 Conclusion and Future Perspectives
		References
	9: Multifunctional Mesoporous Silica Nanoparticles for Biomedical Applications
		9.1 Introduction
		9.2 Potential Biomedical Application of MSNs
			9.2.1 Multifunctional MSN for Delivery of Therapeutic Agents
			9.2.2 Biomedical Imaging with Multifunctional MSNs
				9.2.2.1 Optical Imaging with MSNs
				9.2.2.2 Positron Emission Tomography (PET)
				9.2.2.3 Magnetic Resonance Imaging (MRI)
			9.2.3 Tissue Regeneration and Wound Healing
			9.2.4 Antimicrobial Applications
		9.3 Conclusion and Future Prospects
		References
	10: Advances in Pulmonary Nanomedicine for Therapeutic Management of Respiratory Diseases
		10.1 Introduction to Nanomedicine
		10.2 Respiratory Diseases and Infections
		10.3 Pulmonary Delivery Systems
			10.3.1 Inhalation Therapy
				10.3.1.1 Macro- and Microstructure of Lungs and Mechanism of Deposition from Inhalation
				10.3.1.2 Mechanism of Particle Deposition
				10.3.1.3 Pulmonary Clearance
			10.3.2 General Consideration for Effective Inhalation Therapy
			10.3.3 Nanomedicines for Targeted Therapy to Lung Cancer
		10.4 Potential Limitations of Pulmonary Delivery
		10.5 Nanomedicines Used Diagnosis, Treatment, and Prevention of Respiratory Diseases
			10.5.1 Nanoparticles
			10.5.2 Dendrimers
			10.5.3 Liposomes
			10.5.4 Lipid-Based Nanoparticles
			10.5.5 Lipid-Polymer Hybrid Nanoparticles
			10.5.6 Micelles
			10.5.7 Magnetic Core-Shell Nanoparticles
			10.5.8 Mesoporous Silica Nanoparticle
		10.6 Limitation/Potential Risk of Nano-Based Formulations
		10.7 Summary and Future Prospects
		References
	11: Nanoemulsion Delivery of Herbal Products: Prospects and Challenges
		11.1 Nanoemulsion Systems for Drug Delivery
		11.2 Herbal-Based Nanoemulsion System
			11.2.1 Previous Research Studies on Herbal Nanoemulsions
		11.3 Challenges and Advantages of Herbal Nanoemulsion Products
		11.4 Applications of Herbal Nanoemulsions
			11.4.1 In Drug Delivery
				11.4.1.1 Passive and Active Tumor Targeting
				11.4.1.2 Topical/Transdermal Delivery
				11.4.1.3 Oral Delivery
				11.4.1.4 Ocular Delivery
				11.4.1.5 Nose-to-Brain Delivery
			11.4.2 Management of Vector-Borne Disease
			11.4.3 In the Food Industry
		11.5 Safety and Regulatory Issues of Herbal Nanoemulsions
			11.5.1 Bioassays and Standardization of Herbal Drugs
			11.5.2 Safety Consideration
			11.5.3 Production and Quality Control
		11.6 Future Prospects of Nanoemulsion-Based Herbal Drug Delivery
			11.6.1 Macrophage-Targeted Vaccine Delivery
			11.6.2 Vascular Imaging and Drug Delivery
			11.6.3 Nanoemulsions in the Food Industry
			11.6.4 Nanoemulsions as Antiageing Formulations
			11.6.5 Fundamental Toxicology Research
		11.7 Conclusion
		References
	12: Stimuli-Responsive Polymers for Cancer Nanomedicines
		12.1 Introduction
		12.2 Physically Dependent Stimuli-Responsive Polymers
			12.2.1 Temperature-Responsive Polymers
			12.2.2 Light-Responsive Polymers
			12.2.3 Electro-Responsive Polymers
		12.3 Chemically Dependent Stimuli-Responsive Polymers
			12.3.1 pH-Responsive Polymers
			12.3.2 Ion-Responsive Polymers
			12.3.3 Redox-Responsive Polymers
		12.4 Biologically Dependent Stimuli-Responsive Polymers
			12.4.1 ROS-Responsive Polymers
			12.4.2 Hypoxia-Responsive Polymers
			12.4.3 Enzyme-Responsive Polymers
		12.5 Dual or Multiple Stimuli-Responsive Polymers
			12.5.1 pH- and Temperature-Responsive Polymers
			12.5.2 pH- and Redox-Responsive Polymers
			12.5.3 Triple Stimuli-Responsive Polymers
		12.6 Brief Description of Some Common Stimuli-Responsive Polymers
			12.6.1 Poly (N-Isopropylacrylamide) (PNiPAAm)
			12.6.2 Poly (N-Vinylcaprolactam) (PNVC)
			12.6.3 Poly (Methyl Vinyl Ether) (PMVE)
			12.6.4 Chitosan
			12.6.5 Pullulan
			12.6.6 Poly(N-Ethyl Oxazoline) PEtOx
		12.7 Stimuli-Responsive Polymeric Nanoformulations for Cancer Therapy
		12.8 Challenges in Developing SRP-Based Nanomedicines Against Cancer
		12.9 Conclusion and Future Perspectives
		References
	13: Carbohydrate-Derived Tailorable Interfaces: Recent Advances and Applications
		13.1 Introduction
		13.2 Some Examples of Carbohydrates and Their Classification
		13.3 Applications of Carbohydrate-Based Functional Interfaces in Nanomedicine
			13.3.1 Functionalization of Carbohydrate Nanocarriers
			13.3.2 Carbohydrates as Full Construction Agents: Synthesis and Applications of Nanogels and Microgels
		13.4 Carbohydrate-Based Smart Delivery Systems: Basics of Targeted Delivery
		13.5 Concluding Remarks
		References
	14: Multifunctional Nanoscale Particles for Theranostic Application in Healthcare
		14.1 Introduction
		14.2 Different Multifunctional Nanocarriers Used as Theranostic System
			14.2.1 Polymer Conjugates
			14.2.2 Dendrimers
			14.2.3 Polymeric Micelles
			14.2.4 SPIONs
			14.2.5 Quantum Dots
			14.2.6 Carbon Dots (Graphene Quantum Dots)
			14.2.7 Gold Nanostructures
			14.2.8 Stimuli Responsive
				14.2.8.1 Temperature Sensitive
				14.2.8.2 pH Sensitive
				14.2.8.3 Ultrasound Responsive
		14.3 Conclusions
		References
	15: Ligand Nanoparticle Conjugation Approach for Targeted Cancer Chemotherapy
		15.1 Introduction
		15.2 Characteristics of Cancer Cells
		15.3 Physiological Hindrance of Cancer Cell Targeting
		15.4 Strategies of Cancer Cell Targeting
			15.4.1 Cancer Cell Targets and Targeting Ligands
			15.4.2 G protein-Coupled Receptors
				15.4.2.1 Bombesin (Bn) Receptors
				15.4.2.2 Somatostatin Receptors
				15.4.2.3 Endothelin Receptors
			15.4.3 Integrin Receptors
				15.4.3.1 Integrin αvbeta3
				15.4.3.2 Integrin α-3
			15.4.4 Folate Receptors
			15.4.5 Transferrin Receptors
			15.4.6 LDL Receptor
			15.4.7 Epidermal Growth Factor Receptors
			15.4.8 Fibroblast Growth Factor Receptors
			15.4.9 Sigma Receptors
		15.5 Conjugation Strategies to Functionalize Nanocarriers
			15.5.1 Covalent Method of Conjugation
			15.5.2 Physical Adsorption Methods
		15.6 Cell Internalization of Nanocarriers
		15.7 Conclusion and Prospects
		References
	16: Tunable Biopolymeric Drug Carrier Nanovehicles and Their Safety
		16.1 Introduction
		16.2 Design of Biopolymeric Nanovehicles
			16.2.1 Polysaccharide-Derived Nanocarriers
			16.2.2 Proteins/Polypeptide-Based Nanocarriers
			16.2.3 Polyphenol-Based Nanocarriers
			16.2.4 Others Nanocarriers Derived from Small Biological Molecules
		16.3 Drug Loading and Release Studies for Biopolymeric Nanovehicles
			16.3.1 Physical Drug Loading and Release
			16.3.2 Chemical Drug Loading and Release
			16.3.3 Loading by Encapsulation/Entrapment and Release
		16.4 Clinical Application and Safety of Therapeutic Carrier Nanovehicles
		16.5 Concluding Remark
		References
	17: Nanomedicine for Challenging Solid Tumors: Recent Trends and Future Ahead
		17.1 Introduction
			17.1.1 Stages of Tumor Development
			17.1.2 Epidemiology
			17.1.3 Risk Factors
			17.1.4 Pathophysiology
		17.2 Treatment
			17.2.1 Other Potential Targeted Therapies
		17.3 Current Challenges
			17.3.1 Tumor Challenges and Nanoformulations to Overcome It
				17.3.1.1 Tumor Interstitial Fluid Pressure (TIFP)
				17.3.1.2 Tumor Microenvironment Challenges
					Low Tumor pH
					Tumor Hypoxia
				17.3.1.3 Angiogenesis and Vascular Disrupting Agent (VDA)
				17.3.1.4 Active and Passive Tumor Targeting
				17.3.1.5 Multidrug-Resistance
			17.3.2 Nanoformulations to Treat Different Cancers
		17.4 Conclusion
		References
Part III: Regulatory, Safety and Marketing Aspects of Nano Medicine
	18: Recent Trends for Nanomedicine Safety
		18.1 Introduction
		18.2 Polymeric Drug Nanocarriers
		18.3 Liposomal Drug Nanocarriers
		18.4 Nanocrystal Drug Nanocarriers
		18.5 Micelle Nanocarriers
		18.6 Protein-Based Nanocarriers
		18.7 Dendrimers
		18.8 Other Nanocarriers
			18.8.1 Carbon Nanotubes
			18.8.2 Metal and Metal Oxide Nanoformulations
		18.9 Toxicity Aspect of Nanomaterials
			18.9.1 Neurotoxicity
			18.9.2 Cardiotoxicity
			18.9.3 Pulmonary Toxicity
			18.9.4 Hemotoxicity
			18.9.5 Hepatotoxicity and Nephrotoxicity
			18.9.6 Genotoxicity
			18.9.7 Methods of Assessment of Toxicity of Nanomaterials
		18.10 Theranostic Applications of Nanomedicines
			18.10.1 Drug-Polymer Conjugate
			18.10.2 Polymers, Liposomes, Micelles, and Dendrimers
			18.10.3 Noble Metal Nanoparticles
			18.10.4 Quantum Dots (QDs)
			18.10.5 Carbon nanotubes
		18.11 Nanomedicines in Clinical Trials
		18.12 Regulatory Authorities for Monitoring Nanomedicines and Their Adverse Effects and Safety Concerns
		18.13 Conclusion
		References
	19: Nanotoxicity and Risk Assessment of Nanomedicines
		19.1 Introduction
		19.2 Nanotoxicology
			19.2.1 Nanomaterial Cellular Uptake
				19.2.1.1 Nasal Route
				19.2.1.2 Gastrointestinal Uptake
				19.2.1.3 Skin Uptake
			19.2.2 Factors Influencing Nanotoxicity
				19.2.2.1 Size
				19.2.2.2 Morphology
				19.2.2.3 Surface of Nanomaterial
			19.2.3 Materials
			19.2.4 Underlying Mechanisms Behind NP-Mediated Toxicity
				19.2.4.1 Oxidative Stress
				19.2.4.2 Autophagy and Disruption of Lysosomal Function
				19.2.4.3 Necrosis and Apoptosis (Cell Death)
		19.3 Risk Assessment
		19.4 Conclusion
		References
	20: Clinical Toxicity of Nanomedicines
		20.1 Nanomaterials in Medicine: Nanomedicine
			20.1.1 Biodegradable or Nonbiodegradable NPs
			20.1.2 Bioactive or Carrier Function of Nanoparticles in NMs
		20.2 Clinical Toxicity of NMs
		20.3 Factors Responsible for Clinical Toxicity of NMs
			20.3.1 Physicochemical Properties
				20.3.1.1 Effect of Size, Surface Area, and Shape
				20.3.1.2 Effect of Surface Charge and Coating
				20.3.1.3 Effect of Composition and Degradability
				20.3.1.4 Other Factors
			20.3.2 Route of Administration
				20.3.2.1 Systemic Routes of Administration
					Intravenous
				20.3.2.2 Slow Absorbing Systemic Routes of Administration
					Oral
					Respiratory Tract
					Skin
				20.3.2.3 Route for Local Delivery at Diseased Site
		20.4 Clinical Insights into the Mechanism of NM Toxicity
			20.4.1 Cellular Mechanism
			20.4.2 Subcellular Mechanisms
			20.4.3 Molecular Mechanisms
		20.5 Models for Assessing Toxicity
			20.5.1 Cell-Based Models
				20.5.1.1 2D Cell Culture Models: A High-Throughput Screening Approach
				20.5.1.2 3D Monoculture and Coculture Models: Physiological Relevance
			20.5.2 Animal Models for Toxicity Testing
				20.5.2.1 Small Animal Models
				20.5.2.2 Nonhuman Primate Models
		20.6 Regulatory Guidelines for Clinical Toxicity of NMs
			20.6.1 Some of the Challenges Associated with Nanomaterial Regulation Are [107, 108]
			20.6.2 Current Global Regulatory Status
		20.7 Summary and Challenges
		20.8 Future Prospects
		References
	21: Nanomedicine: Risk, Safety, Regulation, and Public Health
		21.1 Introduction
			21.1.1 NanoMedicine
		21.2 Growing Areas for Nanomedicines
		21.3 Nanomedicine: Known and Unknown Risks
		21.4 Risks for Nanomedicines
		21.5 Nanomedicines in Biological Systems
		21.6 Route-Specific Issues Related to Inhalation
		21.7 Route-Specific Issues Related to Subcutaneous Sensitization
		21.8 Route-Specific Issues Dermal
			21.8.1 Increased Dermal and Systemic Bioavailability
		21.9 Other Safety Issues Due to Nanoparticle Exposure
		21.10 Possibilities of Nanoparticle Exposure in Industrial Setting
		21.11 Occupational Hazards After Nanoparticle Exposure
		21.12 Nanomedicine and the Pharmacokinetic and Pharmacodynamic Considerations
		21.13 Regulations of Nanoproducts and Nanomedicines
		21.14 Challenges Ahead for the Regulatory Bodies
		21.15 US FDA Guidance Document 2011
		21.16 US FDA Center for Drug Evaluation and Research (CDER) Guidelines for Nanoproducts
		21.17 The Center for Veterinary Medicine (CVM) Guidelines
		21.18 The Center for Food Safety and Applied Nutrition (CFSAN) Guidelines
		21.19 CFSAN on Food and Food Packaging Guidance
		21.20 Environmental Protection Agencies (EPA) and Toxic Substances Control Act (TSCA) Recommendations Adopted by FDA
		21.21 FDA Guidelines on Devices Using Nanotechnology
		21.22 Regulations About Nanoproducts in Other Countries
		21.23 Nanotechnology, Public Health, and Public Opinions
		References
	22: New Deliveries and Nanomedicines: Commercial Aspects and Business Perspectives
		22.1 Overview
		22.2 Basic Economics and Resources
			22.2.1 Profits and Patent Protection
			22.2.2 Patent Expiration: Brands Versus Generics
			22.2.3 Price Controls and After-Tax Returns
		22.3 Drug Repurposing in Pharmaceutical Industry: New Therapeutic Opportunities for Existing Drugs
			22.3.1 Rationale and Approaches of Repurposing
			22.3.2 Reformulation: Key Segment in Pharmaceutical Product Life Cycle Management
		22.4 Prioritization Process for Reformulation Drug Candidates
			22.4.1 Developing Drug Candidates´ List
			22.4.2 Scrutinizing the Delivery Technology
			22.4.3 Analyzing Therapeutic or Administrative Unfulfilled Needs
			22.4.4 Conducting a Competitive Screen
			22.4.5 Mapping the Market
		22.5 Decisive Reformulation Factors
			22.5.1 Extended Patent Life: Brands Versus Generics
			22.5.2 Reduced Patient Noncompliance
			22.5.3 Enhanced Therapeutic Efficacy
			22.5.4 Decreased Manufacturing Costs
			22.5.5 Expanded Market
		22.6 Drug Industry´s Need of ``New Deliveries´´ Approach
			22.6.1 New Presentations
			22.6.2 Extended-Release Formulations
			22.6.3 Fixed-Dose Combinations
			22.6.4 User-Friendly Dosage Forms
			22.6.5 Alternative Routes of Administration
		22.7 Drug Industry´s Need of Miniaturization and Nanotechnology: Evolution and Revolution of Nanomedicine
		22.8 Challenges in Nanomedicines´ Clinical Translation and Commercialization
			22.8.1 Biological Barriers
			22.8.2 Manufacturing and Scale-up Complexities
			22.8.3 Biocompatibility and Toxicity Issues
			22.8.4 Ineffective Patenting
			22.8.5 Inadequate Regulations
			22.8.6 Financial Resources, Profitability, and Overall Cost-Effectiveness
			22.8.7 Generics Market and Insurance Policies
		22.9 New Deliveries and Nanomedicine: Market and Forecast
		22.10 Concluding Remarks
		References
	23: Global Growth of Nanomedicine and What Role it Will Play for Economically Weak Countries
		23.1 Introduction
		23.2 Nanomedicine and its Application
		23.3 Global Market of Nanomedicine
		23.4 Nanomedicine: A Disruptive Innovation
		23.5 Challenges in Global Growth of Nanomedicine
		23.6 Impact on Economically Weak Countries: Pros and Cons
		23.7 Future Prospects of Nanomedicines
		23.8 Conclusion
		References