Biomedical Applications and Toxicity of Nanomaterials

Preface
Contents
Editors and Contributors
1: Macroporous Cryogel-Based Systems for Water Treatment Applications and Safety: Nanocomposite-Based Cryogels and Bacteria-Ba...
1.1 Introduction
1.2 Nanocomposite-Based Cryogels
1.2.1 Nanocomposite Cryogel Preparation
1.2.1.1 Direct method
1.2.1.2 Immobilizing Nanoparticles on the Surface of Cryogels
1.2.1.3 In Situ Preparation
1.2.2 Application of Cryogel Nanocomposites for Water Treatment
1.2.2.1 Adsorption
1.2.2.2 Catalysis
1.2.3 Assessment of the Safety of Nanocomposite Devices
1.2.3.1 Assessment of Nanoparticle Leaching from Nanocomposites
1.2.3.2 Assessment of Nanocomposite Toxicity
1.3 Bacteria-Based Bioreactors
1.3.1 Methods for Bacteria Immobilization
1.3.2 Environmental Applications of Cryogels with Immobilized Bacteria
1.3.3 Sensors for Monitoring Water Quality
1.4 Concluding Remarks
References
2: One-Dimensional Semiconducting Nanomaterials: Toxicity and Clinical Applications
2.1 Introduction
2.2 Fabrication of 1D Semiconductors
2.2.1 Top-Down Fabrication
2.2.2 Vapor-Liquid-Solid (VLS) Phase Growth
2.2.3 Solution-Liquid-Solid (SLS) Method
2.2.4 Vapor-Solid-Solid (VSS) Method
2.2.5 Vapor-Solid (VS) Method
2.2.6 Electrospinning
2.2.7 Electrochemical Deposition
2.2.8 Hydrothermal Synthesis
2.2.9 Chemical Vapor Deposition (CVD)
2.2.10 Intrinsic Growth
2.2.11 Manipulating the Growth Using Capping Agents
2.2.12 Self-Assembly
2.2.13 Template-Assisted
2.2.14 Electrochemical Anodization
2.3 Biocompatibility
2.4 Biomedical Applications
2.4.1 Sensors for Medical Diagnosis
2.4.2 Bone Applications
2.4.3 Phototherapy
2.4.4 Drug Delivery
2.4.5 Other Applications
2.5 Conclusion and Outlook
References
3: Prospects of Safe Use of Nanomaterials in Biomedical Applications
3.1 Introduction
3.2 Biosensors
3.3 Nanomaterials
3.3.1 Surface Functionalization of Nanoparticles
3.4 Cancer Biomarkers
3.4.1 Lanthanum Hydroxide Nanoparticles (La(OH)3) Based Electrochemical Biosensor for Detection of Cyfra-21-1 Cancer Biomarker
3.4.2 Detection of Cyfra-21-1 Cancer Biomarker Using Cubic Cerium Oxide-Reduced Graphene Oxide (CeO2-RGO) Nanocomposite-Based ...
3.4.3 RGO Modified Mediator Paper-Based Electrochemical Biosensor for IL-8 Cancer Biomarker Detection
3.5 Vitamin-D3 Biomarker
3.5.1 Insoluble and Hydrophilic Electro Spun Cellulose Acetate Fiber-Based Electrochemical Biosensor for 25-OHD3 Biomarker Det...
3.6 Carbon Dots (CDs) for Bioimaging Applications in Cancerous Cells
3.7 Conclusion
References
4: Hyaluronic Acid-Based Nanotechnologies for Delivery and Treatment
4.1 Introduction: CD44 and Hyaluronic Acid Interaction
4.1.1 CD44
4.1.2 CD44 Role in Physiological Condition vs Cancer
4.1.3 CD44 expression in normal, inflamed, and cancer tissues
4.1.4 Hyaluronic Acid and Its physiological Role
4.1.4.1 Role of Hyaluronic Acid in inflammation
4.1.4.2 Role of Hyaluronic Acid in Cancer
4.1.5 Internalization of Soluble Hyaluronic Acid
4.1.6 Hyaluronic Acid and Current Treatments
4.1.6.1 Role of Hyaluronic Acid as Therapeutic
4.1.6.2 Ophthalmic and Injectable Hyaluronic Acid Treatments
4.1.6.3 Hyaluronic Acid Conjugates
4.2 Hyaluronic Acid-Based Nanotechnologies to Target CD44
4.2.1 Current Strategies to Manufacture Hyaluronic Acid-Based Nanotechnologies
4.2.2 Hyaluronic Acid-Based Nanoparticles and Design of Experiments
4.2.3 Formulation of Nanoparticles for Delivery of Nucleic Acid to Cancer Cells
4.2.3.1 Chitosan Hyaluronic Acid Nanoparticles and Impact of Formulation and Preparation Processes on Their Characteristics
4.2.3.2 Design Criteria for the Formulation of Nanoparticles to Deliver Nucleic Acids to Target CD44+ Cells
4.2.4 Considerations on the Single-Step Fabrication of Hyaluronic Acid Nanoparticles
4.3 Manufacturing of Chitosan/Hyaluronic Acid Nanoparticles for the Delivery of Nucleic Acids
4.3.1 Current Challenges to Deliver siRNA
4.3.2 Models to Validate Delivery Via CD44: Internalization Mechanisms of Hyaluronic Acid Modified Chitosan Nanoparticles
4.4 Conclusion
References
5: Theranostics Nanomaterials for Safe Cancer Treatment
5.1 Introduction: Cancer and Nanomedicine
5.2 Bio-Inspired Organic Nanoparticles Used in Cancer
5.2.1 Liposomes
5.2.2 Lipid-Based Theranostic Nanoparticles (LNPs)
5.2.3 Solid-Form Lipid Nanoparticles (SLNs)
5.2.4 Lipid-Nano Structure (NLCs)
5.2.5 Lipid-Based Nanocapsules (LNCs)
5.2.6 Lipid Micelles
5.2.7 Protein-Based Theranostic Nanoparticles
5.2.8 Viral Nanoparticles (VNPs)
5.2.9 Oligonucleotide Theranostic Nanoparticles
5.2.10 Peptide Theranostic Nanoparticles
5.3 Inorganic Theranostic Nanoparticles
5.3.1 Gold Theranostic Nanoparticles (AuNPs)
5.3.2 Silver Nanoparticles as Theranostic Agents (AgNPs)
5.3.3 Iron Oxide Nanoparticles
5.4 Conclusion
References
6: Cardiovascular Safety Assessment of New Chemical Entities: Current Perspective and Emerging Technologies
6.1 Introduction and Importance of Cardiovascular Safety Studies
6.2 ICH S7A: Safety Pharmacology Studies for Human Pharmaceuticals
6.2.1 Safety Pharmacology Core Battery
6.2.2 Follow-up Safety Pharmacology Studies
6.2.3 Supplemental Safety Pharmacology Studies
6.3 ICH S7B Guidelines: The Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolon...
6.3.1 hERG Channels and QT Syndrome
6.4 Conventional Techniques for CVS Safety Assessments
6.4.1 In Vivo Telemetry Technique
6.4.2 In Vitro hERG Assay and Isolated Systems
6.5 Emerging Technologies Techniques for CVS Safety Assessments
6.5.1 In Vivo Techniques
6.5.2 In Vitro Techniques
6.6 Newer Concepts in CVS Safety Assessment
6.6.1 Front-Loading
6.6.2 Integrated Core Battery Safety Studies
6.6.3 Introduction of Alternate Models
6.6.4 Exploration of Targets
6.7 Journey to an Evolved CVS Safety Assessment Approach
6.7.1 Application of Cardiac Stem Cells in CVS Safety Studies
6.7.2 Cardiac Slice Preparation (In Vitro)
6.7.3 Advanced and Superior Blood Pressure Recording with High Definition Oscillometry
6.7.4 Cardiac Contractility a Core CVS Study Parameter
6.7.5 Organ on Chips
6.8 ICH E14 Guideline: The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhyth...
6.9 The Downside of the Current Approach on CVS Safety Assessment
6.10 Development of a New Prototype for the Assessment of NCE Cardiovascular Liability
6.11 Comprehensive In Vitro Proarrhythmia Assay (CiPA)
6.12 In Silico Methods of CVS Safety Assessment: The Smart and Mathematical Future
6.13 Conclusion
References
7: Toxicology of Pharmaceutical Products During Drug Development
7.1 Introduction
7.2 Basic Principles of Toxicity Studies
7.3 Role of Preclinical Toxicity Animal Models in Drug Development
7.4 In-vivo Models
7.5 Different Animal Models in Toxicological Studies
7.6 In-vitro Models
7.7 Types of (Systemic) Toxicity Studies: Acute, Subchronic, and Chronic Toxicology
7.8 Fourteen to Twenty-Eight Day Repeated-Dose Toxicity Studies
7.9 Ninety-Day Repeated-Dose Toxicity Studies
7.10 180-Day Repeated-Dose Toxicity Studies
7.11 Female Reproduction and Developmental Toxicity Studies
7.11.1 Segment I-Female Fertility Study
7.11.2 Segment II-Teratogenicity Study
7.11.3 Segment III: Perinatal Study
7.12 Special Toxicities Studies
7.12.1 Local Toxicity
7.12.2 Dermal Toxicity Study
7.12.3 Photo-Allergy or Dermal Phototoxicity
7.12.4 Vaginal Toxicity Test
7.12.5 Rectal Tolerance Test
7.12.6 Ocular Toxicity Studies
7.12.7 Inhalation Toxicity Studies
7.12.8 Allergenicity/Hypersensitivity
7.12.9 Genotoxicity Studies
7.12.10 Carcinogenicity Studies
References
8: Safety and Risk Assessment of Food Items
8.1 Introduction
8.1.1 Chemical Risk Assessment
8.1.1.1 Exposure to Toxic Substances Ingested Through Food
8.1.1.2 Identifying and Characterizing Hazards
8.1.2 Microbiological Risk Assessment
8.1.2.1 Risk Characterization
8.1.3 Application of Risk Assessment in the Context of Target Exposures
8.1.4 Case Studies on Targeted Exposure Assessments
8.1.5 Risk Communication and Risk Perception
8.2 Conclusion
References
9: Nontoxic Natural Products as Regulators of Tumor Suppressor Gene Function
9.1 Introduction
9.2 Cancer Critical Genes
9.2.1 Tumor Suppressor Genes
9.2.2 Cell Cycle Check Points
9.2.3 Cell Cycle Control System
9.2.4 Role of CKIs in the Regulation of Cell Cycle Control
9.2.5 Role of RB in Cell Cycle Control
9.2.6 Role of P53 Protein in Cell Cycle Regulation
9.2.7 Role of APC as a Tumor Suppressor Gene
9.2.8 BRCA1 and BRCA2
9.2.9 PTEN
9.2.10 WT1
9.2.11 VHL
9.2.12 NF1
9.3 Natural Products and its Role in Regulating Tumor Suppressor Genes Function
9.3.1 Honokiol
9.3.2 Triptolide
9.3.3 Lichochalcone A
9.3.4 Acanthopanax gracilistilus
9.3.5 Ginsenosides
9.3.6 Curcumin
9.3.7 Genistein
9.3.8 Sesquiterpenoids
9.3.9 Piperine
9.3.10 Quercetin
9.3.11 Artemisinin
9.3.12 Plumbagin
9.3.13 Thymoquinone
9.4 Conclusion
References
10: Advancements in the Safety of Plant Medicine: Back to Nature
10.1 Introduction
10.2 Relevance of Medicinal Plants/Plant-Derived Products and Challenges
10.3 Quality Control and Modernization of Herbal Product Development
10.4 Chemotaxonomic Approach for Sustainable Use of Natural Resources
10.5 Case Studies on Chemotaxonomic Approach
10.6 Acorus calamus L.
10.7 Gloriosa superba L.
10.8 Tribulus terrestris L.
10.9 Coleus forskohlii Briq
10.10 Costus speciosus (Koen. Ex Retz) Sm
10.11 Ageratum conyzoides L.
10.12 Centella asiatica L. (Urban)
10.13 Integration of Herbal Products in the Mainstream: Policy Regulations
10.14 Emerging Concept of Plant-Based Nano-Formulations: A New Face of Traditional Ayurvedic Bhasmas
10.15 Conclusion
References
11: Chemicals and Their Interaction in the Aquaculture System
11.1 Introduction
11.2 Chemical Practices in Aquaculture Systems
11.3 Aquaculture Species of Commercial Importance: Worldwide Review
11.4 Chemical Ingredients Purposed for Water Quality Management in Aquaculture
11.4.1 Liming
11.4.2 EDTA treatment
11.4.3 Potassium Permanganate treatment
11.5 Fertilizers
11.6 Disinfectants
11.6.1 Chlorination
11.6.2 Formalin Treatment
11.6.3 BKC Treatment
11.6.4 Iodine Treatment
11.6.5 Hydrogen Peroxide
11.6.6 Malachite Green
11.7 Anesthetics
11.8 Chemical Structure of Benzocaine
11.9 Antimicrobials
11.9.1 Chloramphenicol
11.9.2 Acriflavine
11.9.3 Copper Compound
11.9.4 Dipterex
11.10 Feed Additives
11.11 Pesticides
11.11.1 Herbicides
11.11.2 Insecticides
11.12 Immunostimulants
11.13 Breeding Inducing Agents
11.14 Conclusion
References
12: Zebrafish as a Biomedical Model to Define Developmental Origins of Chemical Toxicity
12.1 Introduction
12.2 Mechanisms of the DOHaD Paradigm
12.3 Overview of DOHaD Studies in Environmental Health
12.4 Strengths of the Zebrafish to Address the DOHaD of Environmental Chemicals
12.5 DOHaD Toxicity Studies Using Zebrafish
12.6 Study Design Considerations
12.7 Future Directions and Challenges
References
13: Green Synthesis of Nontoxic Nanoparticles
13.1 Introduction
13.2 Synthesis of Nanoparticles Using a Green Approach
13.3 Nanoparticle Synthesis Mediated by Bacteria
13.4 Nanoparticle Synthesis Mediated by Fungus and Yeast
13.5 Nanoparticle Synthesis Mediated by Algae
13.6 Nanoparticle Synthesis Mediated by Viruses
13.7 Nanoparticle Synthesis Mediated by Plants
13.8 Factors Affecting the Biosynthesis of Nanoparticles
13.9 Characterization of the Synthesized Nanoparticle
13.10 Safety Aspects of Green Synthesized Nanoparticles
13.11 Application of Nanoparticles Developed by Green Synthesis
13.12 Conclusion and Future Perspectives
References
14: Synthesis, Characterization and Applications of Titanium Dioxide Nanoparticles
14.1 Introduction
14.2 Methods for Synthesis of TiO2 Nanoparticles
14.2.1 Physical Methods
14.2.1.1 Spray Pyrolysis Synthesis and Electrophoretic Concentration of TiO2 NPs
14.2.1.2 Microwave-Assisted Method for Synthesis
14.2.1.3 Laser Ablation
14.2.1.4 Electrochemical Method
14.2.2 Chemical Methods
14.2.2.1 Sol-Gel Route of Synthesis
14.2.2.2 Coprecipitation Method
14.2.2.3 Solvothermal Method
14.2.2.4 Hydrothermal Method
14.2.2.5 Laser Vaporization and Condensation
14.2.3 Biological Methods
14.3 Characterization
14.4 Applications
14.5 Industrial Application
14.5.1 Lithium Batteries
14.5.2 Gas Sensors
14.5.3 Paper Industry
14.5.4 Food Industry
14.6 Environmental
14.6.1 Photocatalyst
14.6.2 Photocatalytic Elimination of Water Pollutants
14.6.3 Removal of Pollution/Deodorization Applications
14.7 Biomedical Application
14.7.1 Photodynamic Therapy (PDT)
14.7.2 Targeted Drug Delivery
14.7.3 Antibacterial Activity
14.7.4 Bone and Dental Implants
14.8 Conclusion
References
15: Characterization of Nontoxic Nanomaterials for Biological Applications
15.1 Introduction
15.2 Physical and Morphological Characterization
15.2.1 Scanning Electron Microscopy (SEM)
15.2.2 Transmission Electron Microscope (TEM)
15.2.3 Brunauer-Emmett-Teller (BET) Surface Area Analysis
15.2.4 Atomic Force Microscopy (AFM)
15.3 Chemical and Biological Characterization
15.3.1 X-Ray Diffraction (XRD)
15.3.2 Inductively Coupled Plasma Mass Spectrometry (ICP-MS)
15.3.3 X-Ray Photoelectron Spectroscopy (XPS)
15.3.4 Dynamic Light Scattering (DLS)
15.3.5 X-Ray Absorption Spectroscopy (XAS)
15.4 Spectral Characterization
15.4.1 UV-VIS Spectroscopy
15.4.2 Fourier Transform Infrared Spectroscopy (FTIR)
15.4.3 Nuclear Magnetic Resonance Spectroscopy (NMR)
15.4.4 Electron Spin Resonance Spectroscopy (ESR)
15.4.5 Mossbauer Spectroscopy
15.5 Thermal Characterization
15.5.1 Thermogravimetric Analysis (TGA)
15.5.2 Differential Scanning Calorimetry (DSC)
15.5.3 Differential Thermal Analysis (DTA)
15.6 Optical Characterization Techniques
15.6.1 Photoluminescence Spectroscopy
15.6.2 UV-Visible Spectroscopy
15.6.3 Infrared (IR) Spectroscopy
15.6.4 Raman Spectroscopy
15.7 Magnetic, Rheological, and Electrical Characterization
15.7.1 Magnetic Characterization
15.7.2 Rheological Characterization
15.7.3 Electrical Characterization
15.8 Conclusion
References
16: Toxicity Assessment of Nanoparticle
16.1 Introduction
16.2 Potential Mechanism of Nanoparticle-Induced Toxicity
16.3 Toxicity Assessments
16.3.1 In Vitro Toxicity Assessment
16.3.1.1 MTT Assay
16.3.1.2 Modified Tetrazolium Salts
16.3.1.3 Neutral Red Uptake Assay
16.3.1.4 Lactate Dehydrogenase Assay
16.3.1.5 Sulforhodamine B Assay
16.3.1.6 Resazurin Reduction Assay
16.3.1.7 Assay of Intracellular ATP
16.3.1.8 Calcein-AM/PI Dual Staining
16.3.2 In Vivo Toxicity Assessments
16.3.2.1 Embryonic Zebrafish Assay
16.3.2.2 Reproductive Toxicity Assessment Using Drosophila melanogaster
16.3.2.3 Toxicity Assessment Using Daphina magna
16.3.2.4 Chick Chorioallantoic Membrane (CAM) Assay
16.3.2.5 Acute and Chronic Toxicity Studies
16.3.2.6 Micronucleus Assay
16.3.2.7 Chromosomal Aberrations Assay
16.3.2.8 DNA Damage Assay
16.3.2.9 Immunotoxicity Assays
16.3.2.10 Buehler Test (BT)
16.3.2.11 The Guinea Pig Maximization Test (GPMT)
16.3.2.12 Local Lymph Node Assay (LLNA)
16.4 Challenges and Future Perspective in Toxicity Assessment of Nanoparticles
References
17: Safety of Nanoparticles: Emphasis on Antimicrobial Properties
17.1 Introduction
17.2 Nanoparticles: An Overview
17.2.1 Nanoparticles as Drug Carriers
17.2.1.1 Chitosan
17.2.1.2 Alginate
17.2.1.3 Liposomes
17.2.1.4 Solid Lipid Nanoparticles
17.2.1.5 Polymeric Nanoparticles
17.2.1.6 Dendrimers
17.2.1.7 Quantum Dots
17.2.1.8 Metallic Nanoparticles
17.2.1.9 Carbon-Based Nanoparticles
17.2.2 Advantages of Drug Administration Employing Nanoscience
17.2.3 Disadvantages of Drug Administration Employing Nanoscience
17.3 Applications of Nanoparticles
17.3.1 Nanoparticles as Antibacterial Agents
17.3.2 Nanoparticles as Antifungal Agents
17.3.3 Nanoparticles as Antiviral Agents
17.3.4 Nanoparticles as Anti-leishmanial Agents
17.4 Conclusion and Future Perspectives
References
18: Quantum Dots for Imaging and Its Safety
18.1 Introduction
18.2 Features of QDs
18.2.1 Tunable Light Emission
18.2.2 Broad Absorption Spectra and Narrow Emission Spectra
18.2.3 High Quantum Yield and High Absorption Extinction Coefficient
18.2.4 Excellent Photostability
18.3 Synthesis of Quantum Dots
18.4 Classification/Types of Quantum Dots
18.5 Imaging Applications of Quantum Dots
18.5.1 In Vitro Imaging
18.5.1.1 Cellular and Biomolecular Imaging
18.5.1.2 Tissue Staining
18.5.1.3 Binding Assays
18.5.2 In Vivo Imaging
18.5.2.1 Tumor Imaging
18.5.2.2 Deep Tissue Imaging
18.6 Safety Concerns of QDs
18.7 Conclusion
References
19: Genotoxicity Evaluation of Nanosized Materials
19.1 Introduction
19.2 Genotoxicity Evaluation of Nanomaterials
19.3 Mutagenicity Assay
19.3.1 In Vitro Mutagenicity
19.3.1.1 The Ames Test
19.3.2 In Vitro Mammalian Cell Gene Mutation Test
19.3.2.1 Hypoxanthine-Guanine Phosphoribosyl Transferase Test
19.3.2.2 Xanthine-Guanine Phosphoribosyl Transferase Test
19.3.2.3 The In Vitro Mouse Lymphoma Assay (Mutation at Tk Gene)
19.3.3 In Vivo Mammalian Mutagenicity Assay
19.3.3.1 LacI and LacZ Transgenic Mouse Model (Somatic Cells)
19.3.3.2 Transgenic Rodent Assays (Germ Cell)
19.3.3.3 Pig-a Assay in Rodents and Humans
19.4 Chromosomal Damage Assays
19.4.1 Single Cell Gel Electrophoresis (SCGE) Assay/Comet Assay
19.4.2 General Requirements
19.4.3 In Vitro Comet Assay
19.4.3.1 Alkaline Single Cell Gel Electrophoresis/Alkaline Comet Assay
19.4.3.2 Preparation of Sample
19.4.3.3 Preparation of Slides for Electrophoresis and Visualization of Comets
19.4.4 In Vivo Comet Assay
19.4.4.1 Selection of Animals and Experimental Design
19.4.4.2 Dose Selection, Administration, and Sampling
19.4.4.3 Preparation of Sample and Work Procedure
19.4.4.4 Analysis and Interpretation
19.5 Micronucleus Assay
19.5.1 In Vitro Mammalian Cell Micronucleus (MN) Assay
19.5.1.1 General Principle
19.5.1.2 Experimental Design
19.5.1.3 Experimental Procedure
19.5.1.4 Analysis and Interpretation of In Vitro Micronucleus Assay
19.5.2 In Vivo MN Assay
19.5.2.1 Experimental Design and General Requirements
19.5.2.2 Analysis and Interpretation of In Vivo Micronucleus Assay
19.6 Chromosomal Aberration Assay
19.6.1 In Vitro Chromosomal Aberration Test
19.6.1.1 Selection and Preparation of Sample
19.6.1.2 Chromosome Harvest and Analysis
19.6.2 In Vivo Chromosomal Aberration Test
19.6.2.1 Experimental Design and Sample Preparation
19.6.2.2 Chromosome Harvest Analysis and Interpretation
19.7 DNA Damage
19.7.1 Double-Strand Breaks (DSB) Assay
19.8 High-ThroughPut Methods and Recent In Vitro Models
19.8.1 Modified Versions of the Comet Assay
19.8.1.1 Medium Throughput Methylation-Sensitive Comet Assay
19.8.1.2 Endo III and FPG-Modified Comet Assay
19.8.1.3 Comet-FISH
19.8.1.4 High-Throughput Screening Using Comet Chip
19.8.1.5 ToxTracker Assay
19.8.2 Modified Techniques for MN Detection
19.8.2.1 Flow Cytometry Method
19.8.2.2 In Vitro Micronucleus Assay and FISH Analysis
19.9 Advantages and Limitations of Genotoxicity Assays
19.10 General Mechanisms of Genotoxicity
19.10.1 Primary Genotoxicity
19.10.2 Secondary Genotoxicity
19.11 Conclusion
References
20: Scaffold Materials and Toxicity
20.1 Introduction
20.2 Various Scaffold Materials and Their Possible Toxicity
20.2.1 Synthetic Scaffolds Materials
20.2.2 Natural Products Scaffold Materials
20.3 Advances in Scaffold Engineering: Nanoscaffolds and Related Toxicity
20.4 Toxicity Evaluation Tests of Scaffolds
20.5 Conclusion
References
21: Biological Safety and Cellular Interactions of Nanoparticles
21.1 Introduction
21.2 The Dynamics of Nanoparticle-Cell Interaction
21.2.1 Cellular Internalization of Nanoparticles
21.2.2 Interaction of Nanoparticles with Tumor Tissue
21.3 Cellular Pathways for Nanoparticle Uptake
21.3.1 Phagocytosis
21.3.2 Macropinocytosis
21.3.3 Clathrin-Mediated Endocytosis
21.3.4 Caveolae-Mediated Endocytosis
21.3.5 Clathrin- and Caveolin-Independent Endocytosis
21.4 Physicochemical Properties of Nanoparticles Influencing the Interaction Mechanisms
21.4.1 Size
21.4.2 Shape
21.4.3 Charge and Surface Hydrophobicity
21.5 The Cell Mechanics Influencing Nanoparticle-Cell Interaction
21.5.1 Cellular Adhesion
21.5.2 Cytoskeleton Interactions
21.6 Cell-Nanoparticle Interactions and Hemostasis
21.6.1 The Formation of Protein Corona
21.6.2 Nanoparticles and the Interaction with Blood Cells
21.7 Intracellular Trafficking of NPs
21.7.1 Endosomal Escape
21.7.2 Organelle and Subcellular Targeting
21.7.3 Exocytosis
21.8 Cell-Nanoparticle Interactions and Cytotoxicity
21.9 Exploring the Cellular Interaction of Nanoparticles
21.10 Conclusion
References
22: Role of Artificial Intelligence in the Toxicity Prediction of Drugs
22.1 Introduction
22.1.1 Toxicity Due to Chemicals and Drugs
22.1.2 Artificial Intelligence
22.1.3 Machine Learning Models
22.1.4 Algorithms
22.1.5 Performance Evaluation Measures
22.1.6 Machine Learning Model Development
22.2 Tools Used in Artificial Intelligence
22.2.1 Neural Networks
22.2.2 Deep Learning Frameworks and Libraries
22.2.2.1 Cafe
22.2.2.2 Theano
22.2.2.3 TensorFlow
22.2.2.4 Torch
22.2.2.5 PyTorch
22.2.2.6 Scikit-Learn
22.2.3 Quantitative Structure-Activity Relationship (QSAR)
22.2.3.1 Descriptors Based on a Different Dimension
22.2.3.2 Model-Based QSAR Approach
22.2.3.3 3D QSAR
22.2.3.3.1 Comparative Molecular Field Analysis (CoMFA)
22.2.3.3.2 Comparative Molecular Similarity Indices Analysis (CoMSIA)
22.2.3.4 Machine Learning in QSAR
22.2.3.5 Application of QSAR
22.2.4 Docking
22.2.4.1 Steps in Molecular Docking
22.2.4.2 Different Types of Molecular Docking
22.2.4.3 Machine Learning in Docking
22.2.4.4 Application of Molecular Docking
22.3 OECD Guidelines for Testing Chemicals
22.4 Importance of Artificial Intelligence in Toxicity Predictions
22.4.1 Toxicity Due to Drugs
22.4.2 Toxicity Due to Drug-Drug Interactions
22.4.3 Toxicity Due to Drug-Transporter Interaction
22.5 Prediction of Toxicity in Different Organs by AI
22.5.1 Liver
22.5.2 Heart
22.5.3 Eye and Skin
22.5.4 Gastrointestinal
22.5.5 Kidney
22.6 Conclusion
References
23: Chemicals and Rodent Models for the Safety Study of Alzheimer´s Disease
23.1 The Mouse as an Animal Model System
23.2 Mouse as an Animal Model System for Alzheimer´s Disease (AD) Research
23.2.1 The Amyloid Hypothesis
23.2.2 The Tau Hypothesis
23.2.3 Cholinergic Hypothesis
23.3 Commonly Used Mouse Model Systems to Study AD
23.3.1 Transgenic Mouse Models of AD
23.3.2 Chemical-Induced Models for Studying AD
23.3.2.1 Streptozotocin and AD Development
23.3.2.2 Scopolamine and AD Development
23.3.2.3 Colchicine and AD Model
23.3.2.4 Okadaic Acid and AD Development
23.3.2.5 Sodium Azide-Induced AD Model
23.3.2.6 Heavy Metal-Induced AD-Like Model
23.3.2.7 Alcohol-Induced AD-Like Model
23.3.2.8 Ibotenic Acid-Induced AD Model System
23.3.2.9 LPS-Induced AD Model System
References
24: Mitochondria-Targeted Liposomal Delivery in Parkinson´s Disease
24.1 Introduction
24.2 Mitochondrial Dysfunction and Parkinson´s Disease
24.3 Liposomal Drug Delivery Across the BBB
24.4 Mitochondria-Targeted Liposomal Formulations
24.5 Advantages and Challenges of Liposomal Delivery
24.5.1 Advantages of Liposomes
24.5.2 Challenges of Liposomes
24.6 Regulatory Challenges for Liposomes
24.7 Conclusion
References
25: Routes of Nano-drug Administration and Nano-based Drug Delivery System and Toxicity
25.1 Introduction: Importance of Nanoparticle-Based Drug Delivery
25.2 Routes of Nano-drug Delivery
25.2.1 Oral Route of Drug Delivery
25.2.1.1 Stomach Targeting Drug Delivery
25.2.1.2 Small Intestine Targeting Drug Delivery
25.2.1.3 Colon-Targeted Drug Delivery
25.2.2 Nanocarriers in Oral Route
25.2.2.1 Dendrimers
25.2.2.2 Liposomes
25.2.2.3 Others
25.2.3 The Transdermal Route of Drug Delivery
25.2.3.1 Anatomy of the Skin
25.2.3.2 Drug Transportation Across the Skin
25.2.4 Nanocarriers in Transdermal Route
25.2.5 Methods of Transdermal Drug Delivery
25.2.5.1 The Passive Method of Transdermal Delivery
25.2.5.1.1 Chemical Enhancers
25.2.5.1.2 Prodrugs
25.2.5.1.3 Carriers and Vehicles
Hydrogels
Liposomes
Vaccines
Others
25.2.5.2 The Active Method of Transdermal Delivery
25.2.5.2.1 Electroporation
25.2.5.2.2 Iontophoresis
25.2.5.2.3 Sonophoresis
25.2.5.2.4 Microneedles
25.2.5.2.5 Others
25.2.6 Ocular Route of Drug Delivery
25.2.6.1 Anatomy of the Eye
25.2.7 Nanocarriers in Ocular Route
25.2.7.1 Niosomes
25.2.7.2 Solid Lipid Nanoparticles
25.2.7.3 Inorganic Nanoparticles
25.2.7.4 Others
25.2.8 Nasal Route of Drug Delivery
25.2.8.1 Nose to Brain Targeting
25.2.8.2 Mechanism of Transport to Brain
25.2.9 Nanocarriers in Nasal Route
25.2.10 Pulmonary Route of Drug Delivery
25.2.10.1 Anatomy of Lungs
25.2.10.2 Mechanism of Drug Deposition in Lungs
25.2.11 Nanocarriers in Pulmonary Route
25.2.11.1 Solid Lipid Nanoparticles
25.2.11.2 Polymeric Nanoparticles
25.2.11.3 Others
25.2.12 Parenteral Route of Drug Delivery
25.2.13 Nanocarriers in Parenteral Route
25.2.14 Nanocarriers in Subcutaneous Route
25.2.15 Nanocarriers in Intramuscular Route
25.2.16 Nanocarriers in Intravenous Route
25.3 Future Perspectives
References
26: Green Synthesized Silver Nanoparticles Phytotoxicity and Applications in Agriculture: An Overview
26.1 Introduction
26.2 Capping Agents in Nanotechnology
26.3 Silver Nanoparticles
26.4 Importance of Biosynthesis of AgNPs
26.5 Role of Plants in Green Synthesis of Nanoparticles
26.6 Phytotoxicity Effect
26.7 Applications of Silver Nanoparticles in Agriculture
26.8 Plant Disease Management and Protection
26.9 Nanofertilizers
26.10 Pest Management
26.11 Conclusion
References
27: Status of Safety Concerns of Microplastic Detection Strategies
27.1 Introduction
27.2 Microplastics
27.2.1 Types
27.2.1.1 Sources
27.2.1.1.1 Dust
27.2.1.1.2 Plastic Pellets
27.2.1.1.3 Synthetic Textiles
27.2.1.1.4 Tires and Road Markings
27.2.2 Physiochemical Properties
27.2.2.1 Particle Size
27.2.2.1.1 Surface Chemistry
27.2.2.1.2 Particle Shape
27.2.2.1.3 Surface Area
27.2.2.1.4 Polymer Crystallinity
27.2.2.1.5 Polymer Additives
27.2.2.1.6 Polymer Types
27.3 Separation Methods for Microplastics
27.3.1 Density-Based Approaches
27.3.2 Hydrophobicity-Based Approaches
27.3.3 Size-Based Approaches
27.3.4 Approaches for Nanoparticle Separation
27.4 Methods for Microplastics Detection
27.4.1 Spectroscopy-Based Detection Methods
27.4.1.1 Raman Spectroscopy
27.4.1.2 Infrared (IR) Spectroscopy
27.4.1.3 Fourier Transform Infrared Spectroscopy (FTIR)
27.4.2 Microscopy-Based Detection Methods
27.4.2.1 Scanning Electron Microscopy (SEM)
27.4.3 Mass Spectrometry (MS)-Based Detection Methods
27.4.3.1 Pyrolysis-Gas Chromatography-Mass Chromatography (Py-GC-MS)
27.4.3.2 Thermal Desorption Coupled with Gas Chromatography: Mass Spectrometry (TDS-GC-MS/TED-GC-MS)
27.4.4 Chromatography-Based Detection Methods
27.4.4.1 Size-Exclusion Chromatography (SEC)
27.4.5 Composition-Based Analysis
27.4.5.1 Density Separation with Subsequent C:H:N Analysis
27.4.6 Novel Detection-Based Methods
27.4.6.1 Atomic Force Microscopy (AFM) Coupled to IR or Raman Spectroscopy
27.4.6.2 Dyes
27.5 Factors Affecting MP Detection
27.5.1 Sampling
27.5.2 Size and morphology
27.6 Conclusion
References
28: Impact of Insecticides on Man and Environment
28.1 Introduction
28.2 History of Insecticide
28.3 Classification of Insecticide
28.3.1 Classification Based on Chemical Composition
28.3.1.1 Inorganic Pesticide
28.3.1.2 Synthetic Insecticides
28.3.1.2.1 Organochlorides
28.3.1.2.2 Organophosphates
28.3.1.2.3 Carbamates
28.3.1.2.4 Pyrethrins
28.3.1.2.5 Neonicotinoids
28.3.1.2.6 Biopesticides
28.3.2 Mode of Entry
28.3.2.1 Systemic Pesticides
28.3.2.2 Contact Pesticides
28.3.2.3 Fumigants
28.3.3 Mode of Action
28.4 Environmental Impact of Insecticides
28.5 Impact of Insecticides on Human Health
28.6 Alternative to Synthetic Insecticides
28.7 Conclusion
References