Nanotoxicology: Toxicity Evaluation of Nanomedicine Applications

Cover
Half Title
Title Page
Copyright Page
Dedication
Table of Contents
Preface
Acknowledgments
Editors
Contributors
Chapter 1 Nanomaterials: Types of Nanomaterials and Their Fundamental Physicochemical Properties
	1.1 Introduction to Nanomaterials
		1.1.1 Nanoscale Size Effect
			1.1.1.1 Surface Area and Surface Area to Volume Ratio
			1.1.1.2 Quantum Confinement Effect
		1.1.2 Classification of Nanomaterials
			1.1.2.1 Zero-Dimensional (0-D) Nanostructured Materials
			1.1.2.2 One-Dimensional (1-D) Nanostructured Materials
			1.1.2.3 Two-Dimensional (2-D) Nanostructured Materials
			1.1.2.4 Three-Dimensional (3-D) Nanostructured Materials
		1.1.3 Special Nanomaterials
		1.1.4 Properties of Nanomaterials
	1.2 Bottom-Up and Top-Down Approaches
		1.2.1 Bottom-Up Approach
		1.2.2 Top-Down Approach
	1.3 Synthesis of Nanomaterials by Chemical Methods
		1.3.1 Solvothermal Synthesis
		1.3.2 Photochemical Synthesis
		1.3.3 Sonochemical Synthesis
		1.3.4 Chemical Vapour Deposition (CVD)
		1.3.5 Sol–Gel Process
	1.4 Physicochemical Properties of Nanoparticles with Reference to Biological Systems
		1.4.1 Size and Dispersion Ability
		1.4.2 Shapes
		1.4.3 Surface Charges
		1.4.4 Targeting Mechanism
	References
Chapter 2 Innovations in Nanotechnology for Biomedical Sensing, Imaging, Drug Delivery, and Therapy
	2.1 Introduction
	2.2 Nano-biosensing
		2.2.1 Nano-biosensors
		2.2.2 Nano-biosensors Used for Biomedical Applications
			2.2.2.1 Nanoparticles
			2.2.2.2 Nanowires
			2.2.2.3 Graphene and Carbon Nanotubes
			2.2.2.4 Nanochannels
		2.2.3 Recent Applications and Discoveries of Nano-biosensors in Biomedical Science
	2.3 Nanotechnology in Medical Imaging
		2.3.1 Nanotechnology and Biomedical Imaging
		2.3.2 Nanomaterials Used in Molecular Imaging
			2.3.2.1 Gold Nanoparticles
			2.3.2.2 Quantum Dots
			2.3.2.3 Iron Oxide Nanoparticles
			2.3.2.4 Carbon Nanotubes
			2.3.2.5 Dendrimers
		2.3.3 Recent Advancements and Directives of Biomedical Applications of Nanomaterials in Molecular Imaging
	2.4 Nanomaterials for Drug Delivery and Therapy
		2.4.1 Nano-Drug Delivery and Therapy
		2.4.2 Nanomaterials in Biomedicine Delivery and Therapy
			2.4.2.1 Protein and Polysaccharide Nanoparticles
			2.4.2.2 Liposomes
			2.4.2.3 Dendrimers
			2.4.2.4 Inorganic/Metallic Nanoparticles
			2.4.2.5 Nanocrystals
			2.4.2.6 Carbon Nanotubes
		2.4.3 Recent Advancements and Discoveries of Nanomedicine
	2.5 Conclusion and Future Directives
	References
Chapter 3 Nanomaterials for Drug Delivery
	3.1 Introduction
	3.2 Classification of Nanomaterials
	3.2.1 Organic Type of Nanomaterial
		3.2.1.1 Lipid-Based Nanoparticles
		3.2.1.2 Dendrimers
		3.2.1.3 Carbon Nanomaterials
		3.2.1.4 Polymeric Micelles
	3.2.2 Inorganic Type of Nanomaterials
		3.2.2.1 Quantum Dots
		3.2.2.2 Gold Nanoparticles
		3.2.2.3 Magnetic Nanoparticles
		3.2.2.4 Plasmonic Nanoparticles
		3.2.2.5 Halloysite Nanoclay
	3.2.3 Combined Organic and Inorganic Nanomaterials
	3.3 Conclusion
	Declaration of Interest
	References
Chapter 4 PLGA-Based Nanoparticulate Systems: New Trends in Nanomedicine
	4.1 Introduction
	4.2 Preparation of PLGA-Based NPs
	4.3 Physiochemical Properties of PLGA NPs
	4.4 Fabrication of PLGA-Based Nanocarriers and Their Functionalization
	4.5 PLGA NPs for Drug Delivery to the Brain
	4.6 PLGA NPs for Drug Delivery to the Ear
	4.7 PLGA NPs for Drug Delivery in Cancer Treatment
	4.8 PLGA NPs for Imaging
	4.9 PLGA NPs in Bone Regeneration
	4.10 Degradation of PLGA
	4.11 Future Prospects of PLGA Formulations for Clinical Applications
	4.12 Conclusion
	References
Chapter 5 Employing New Targeted Nanoencapsulation for Alzheimer’s Disease Treatment: A Change for the Better?
	5.1 Introduction
		5.1.1 Historical Viewpoint and Present Picture of Alzheimer’s Disease (AD)
	5.2 Drugs Based on Nanoparticles for Alzheimer’s Disease
	5.3 Types of Nanoparticle-Based Drugs
		5.3.1 Tacrine
			5.3.1.1 Mode of Action of Tacrine
			5.3.1.2 Efficacy of the Drug
			5.3.1.3 Adverse Effects
		5.3.2 Rivastigmine
			5.3.2.1 Mechanism of Action
			5.3.2.2 Efficacy of the Drug
			5.3.2.3 Adverse Effects of the Drug
		5.3.3 D-Penicillamine
			5.3.3.1 Mode of Action
			5.3.3.2 Efficacy of the Drug
			5.3.3.3 Adverse Effects of the Drug
		5.3.4 Clioquinol
			5.3.4.1 Mechanism of Action
			5.3.4.2 Efficacy of the Drug
			5.3.4.3 Adverse Effects
		5.3.5 VEGF (Vascular Epidermal Growth Factor)
			5.3.5.1 Mechanism of Action
			5.3.5.2 Efficacy of the Drug
		5.3.6 Epigallocatechin-3-Gallate (EGCG)
			5.3.6.1 Mode of Action
			5.3.6.2 Efficacy of the Drug
		5.3.7 Estradiol
			5.3.7.1 Mechanism of Action
			5.3.7.2 Efficacy  of the Drug
			5.3.7.3 Lactoferrin
			5.3.7.4 Mechanism of Action
			5.3.7.5 Efficacy of the Drug
	5.4 Conclusion
	References
Chapter 6 Nanomaterials-Assisted Elicitation of Pharmaceutically Important Secondary Metabolites from In Vitro Plant Cell Cultures
	6.1 Introduction
	6.2 Nanomaterial-Mediated Elicitation of Plant Secondary Metabolites Mechanism
	6.3 Biosynthesis of Plant Secondary Metabolites upon Exposure to Nanomaterials
		6.3.1 Alkaloids
		6.3.2 Phenylpropanoids and Terpenoids
		6.3.3 Flavonoids and Phenolics
	6.4 Conclusion and Future Perspective
	References
Chapter 7 Impact of Nanomaterials on Health and Environment
	7.1 Basic Concepts of Nanotechnology
		7.1.1 Synthesis Methods
	7.2 Toxicity of NMs
	7.3 Exposure Routes of NMs
		7.3.1 Inhalation
		7.3.2 Dermal
		7.3.3 Ingestion
	7.4 Overview of Risk Assessment
		7.4.1 Hazard Assessment
			i. Carbon Nanotubes
			ii. C60 Fullerenes
			iii. Quantum Dots
			iv. Iron Oxide Nanostructures
		7.4.2 Dose-Response Assessment
		7.4.3 Exposure Assessment
		7.4.4 Environmental Exposure Assessment
		7.4.5 Risk Characterization
		7.4.6 Safety and Health Hazard Considerations
	7.5 Conclusion and Future Perspective
	References
Chapter 8 Consequences of Nanomaterials on Human Health and Ecosystem
	8.1 Introduction
	8.2 Toxic Effects of Nanoparticles on Health
		8.2.1 Natural Nanoparticles and Their Toxicity to Health
		8.2.2 Engineered Nanoparticles and Their Toxicity to Health
			8.2.2.1 Cytotoxic and Genotoxic Effects
			8.2.2.2 Hepatotoxic and Nephrotoxic Effects
			8.2.2.3 Respiratory and Cardiotoxicity Effects
			8.2.2.4 Dermal Toxic Effects
			8.2.2.5 Some Studies of NPs on Human Health
	8.3 Toxic Effects of Various Nanoparticles on the Environment
		8.3.1 Natural Nanomaterials and Their Toxicity to the Environment
			8.3.1.1 Impact of Atmospheric Nanoparticles
			8.3.1.2 Impact of Naturally Produced NNPs
			8.3.1.3 Impact of Unintentionally Produced NNPs
		8.3.2 Engineered Nanomaterials and Their Toxicity to the Environment
			8.3.2.1 Impact of ENPs on Different Ecosystems
	8.4 Future Prospective
	8.5 Conclusion
	Abbreviations
	References
		Journals
		Book Chapters
		Online Documents
Chapter 9 Conceptual Understanding of the Mechanisms of Nanotoxicity and Safety of Nanomedicines
	9.1 Introduction
	9.2 DNA Damage
	9.3 Cytotoxicity
		9.3.1 Cytotoxicity of Carbon Nanotubes
		9.3.2 Cytotoxicity of Titanium Dioxide Nanoparticles
		9.3.3 Cytotoxicity of Quantum Dots
		9.3.4 Cytotoxicity of Gold Nanoparticles
		9.3.5 Cytotoxicity of Silver Nanoparticles
	9.4 Nanotoxicity and Cellular Death Mechanisms
		9.4.1 Apoptosis
			9.4.1.1 Apoptosis: Effects of Nanoparticles
		9.4.2 Autophagy
			9.4.2.1 Autophagy: The Effects of Nanoparticles
		9.4.3 Necrosis
			9.4.3.1 Necroptosis: Effects of Nanoparticles
	9.5 Oxidative Stress and Inflammation
		9.5.1 Oxidative Stress
		9.5.2 Nanoparticles, Oxidative Stress, and Inflammation
	9.6 Safety of Nanomedicine
		9.6.1 Hazard and Risk Characterization
		9.6.2 Molecular Toxicity
		9.6.3 Cellular Toxicity
		9.6.4 Tissue Toxicity
	9.7 Environmental Safety of Nanomedicine
	9.8 Conclusion
	References
Chapter 10 Insights into the Mechanisms of Nanotoxicity and Evaluation of Nanomaterials
	10.1 Introduction
	10.2 Nanomaterials and Toxicity
		10.2.1 Toxicity Evaluation in In Vitro and In Vivo Models
		10.2.2 Developmental Toxicity
		10.2.3 Neurotoxicity
		10.2.4 Reproductive Toxicity
		10.2.5 Toxicity in Asthma Models
	10.3 Major Pathways of Nanotoxicity
	10.4 Test Assays for Nanotoxicity
	10.5 Conclusions
	Acknowledgments
	References
Chapter 11 Sensors to Monitor and Evaluate the Toxicity of Nanomedicine Applications
	11.1 Introduction
	11.2 Nanomedicines
		11.2.1 Nanomaterials and Nanostructures
		11.2.2 Toxicity Evaluation
	11.3 Conventional Methods for Monitoring and Imaging
		11.3.1 Microscopy
		11.3.2 Cell Culture
		11.3.3 Others
	11.4 Sensors for Detection Nanomedicines
		11.4.1 Chemicals Sensors
		11.4.2 Biosensors
	11.5 Nanosensors
		11.5.1 Nanochemical Sensors
		11.5.2 Nanobiosensors
	11.6 Micro- and Nanofluidics
	11.7 Conclusions and Future Perspectives
	Acknowledgment
	References
Chapter 12 Systems Approaches for Toxicological Assessment of Nanomaterials
	12.1 Introduction to Systems Toxicology
	12.2 Systems Toxicology Technologies
		12.2.1 High-Content Screening
		12.2.2 Omics Technologies
			12.2.2.1 Genomics and Epigenomics
			12.2.2.2 Transcriptomics
			12.2.2.3 Proteomics
			12.2.2.4 Metabolomics
	12.3 Mechanistic Understanding of High-Density Data
		12.3.1 HCS Data Analysis
		12.3.2 Omics Data Analysis
			12.3.2.1 Pathway Analysis
			12.3.2.2 Biological Network Models
	12.4 Systems Toxicology for Nanomedicine
	12.5 Network Impact of Surface-Modified Gold Nanoparticles on Two Model Human Cell Lines
	12.6 Conclusions and Outlook
	References
Chapter 13 Measurement of Oxygen Consumption Rate Based on Fluorescence Intensity and Lifetime as a Strategy to Assess Nanotoxicity
	13.1 Introduction
	13.2 Assays for Nanotoxicity
	13.3 Techniques for Measurement of OCR
	13.4 O[sub(2)] Sensing Techniques
	13.5 O[sub(2)] -Sensitive Fluorescent Dyes
	13.6 Sensing pO[sub(2)] Based on Fluorescence Intensity
	13.7 Sensing pO[sub(2)] Based on Fluorescence Lifetime
	13.8 Time Domain (TD) Approach
	13.9 Frequency Domain (FD) Approach
	13.10 Summary
	References
Chapter 14 Current Knowledge on Toxicity of Nanomaterials: Toxicity Assessment and Impact
	14.1 Introduction
		14.1.1 Classification of Nanomaterials
	14.2 Toxicity Assays for Nanomaterials
		14.2.1 Methods for In Vitro Assessment of Nanotoxicity
			14.2.1.1 Cytotoxicity Assays
			14.2.1.2 Oxidative Stress Assays
		14.2.2 Methods for In Vivo Assessment of Nanotoxicity
			14.2.2.1 Biodistribution
			14.2.2.2 Clearance
			14.2.2.3 Hematology and Serum Chemistry
			14.2.2.4 Histopathology
	14.3 Impact of Nanomaterials on Health and Environment
		14.3.1 Impact of Nanomaterials on Health
			14.3.1.1 Impact of Natural Nanomaterials on Health
			14.3.1.2 Impact of Anthropogenic Nanomaterials on Health
		14.3.2 Impact of Nanomaterials on the Environment
		14.3.3 Fate of Nanomaterials
			14.3.3.1 Effect on Soil Environment
		14.3.4 Mechanism of Nanomaterials Toxicity
	14.4 Conclusions and Future Directions
	Acknowledgment
	References
Chapter 15 The Role of Nanotechnology in the Management of Water Toxicity
	15.1 Introduction
	15.2 Photocatalysis by Nanocatalysts
	15.3 Nanofiltration
	15.4 Nanosorbents
	15.5 Antimicrobial Nanomaterial Treatment
	15.6 Molecularly Imprinted Polymers (MIPs)
	15.7 Conclusions
	Acknowledgments
	References
Chapter 16 Challenges in the Assessment of Nanotoxicity, Recommendations, and Safe-by-Design Nanomedicines to Counter Toxicological Problems
	16.1 Introduction
		16.1.1 Nanotoxicological Classification System
		16.1.2 Physicochemical Parameters for Toxicity Assessment
			16.1.2.1 Size of Nanomaterials
			16.1.2.2 Surface, Surface Coatings, and Charge
	16.2 Challenges in the Assessment of Nanotoxicity
		16.2.1 In Assessing the Toxicity of Nanomaterials
		16.2.2 In Characterization
		16.2.3 Nanotoxicity Assays
			16.2.3.1 Systemic Assessment
			16.2.3.2 Biodistribution
			16.2.3.3 Gastrointestinal System
			16.2.3.4 Pulmonary System
			16.2.3.5 Nervous System
			16.2.3.6 Immune and Reproductive System
		16.2.4 Identifying the Risk Factors
			16.2.4.1 Difficulties in the Determination of the Mechanism of Nanotoxicity
	16.3 Recommendations and Regulatory Guidelines for Nanoparticle Toxicology
	16.4 Safe by Design Nanomedicines
		16.4.1 Safety of Nanoparticles
		16.4.2 Safety of Nanomedicines
		16.4.3 Testing the Safety of Nanomedicines
	16.5 Usage and Management of Nanoparticles
	16.6 Toxicological Problems
		16.6.1 Toxicological Problems Relating to Changes in the Environment
			16.6.1.1 Long-Term Effects of Environmental Toxins
			16.6.1.2 Effect of Heavy Metal Contamination
	16.7 Metal Oxide Nanoparticles
	16.8 Conclusions
	Author Contributions
	Declaration of Competing Interest
	Acknowledgment
	References
Chapter 17 Current Guidelines and Regulatory Challenges, Insight into the Legal, Societal, and Ethical Issues of Nanomaterials
	17.1 Introduction
	17.2 Status of Nanotechnology in India
		17.2.1 Research Initiatives
		17.2.2 Educational Initiatives
	17.3 Outcomes of Nanotechnology Research
	17.4 Societal Impacts of Nanotechnology
	17.5 Potential Benefits and Associated Risks
	17.6 Civil Liberties and Social Justice
	17.7 Ethics
	17.8 Guidelines
		17.8.1 Hazard Identicat fi ion
		17.8.2 Exposure Pathways and Common Tasks
		17.8.3 Exposure Control Strategies
	17.9 Good Laboratory Practices
	17.10 Future Scope
	Conflict of Interests
	References
Index