دانلود کتاب Drug Delivery with Targeted Nanoparticles: In Vitro and In Vivo Evaluation Methods

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Cover Title Page Copyright Page Table of Contents Preface Chapter 1: Particle Size Determination of Targeted Nanoparticles 1.1: Introduction 1.2: Nanotechnology 1.3: Nanoparticles 1.4: Targeted Nanoparticles 1.5: Particle Size Distribution 1.6: Particle Size Determination Methods 1.6.1: Photon Correlation Spectroscopy/Dynamic Light Scattering 1.6.2: Laser Light Diffraction 1.6.3: X-Ray Diffraction Peak Broadening Analysis 1.6.4: Scanning Electron Microscopy 1.6.5: Transmission Electron Microscopy 1.6.6: Atomic Force Microscopy 1.6.7: Other Methods 1.7: Conclusion Chapter 2: Zeta Potential Determination of Targeted Nanoparticles 2.1: What Is Zeta Potential? 2.2: Determination Methods 2.2.1: Measuring the ZP by Electrophoresis 2.2.2: Tunable Resistive Pulse Sensing 2.3: Characteristics of the ZP 2.3.1: pH 2.3.2: Ionic Strength 2.3.3: Size Effect 2.3.3.1: Present charge 2.3.3.2: Conductivity 2.3.3.3: Concentration 2.3.3.4: Dilution 2.3.3.5: Stability 2.3.3.6: Reproducibility 2.3.3.7: Population 2.3.3.8: Pores and surface coating 2.3.3.9: Size 2.3.3.10: Temperature 2.4: Golden Standards and General Protocol for ZP Measurement 2.4.1: Reagents and Dispersants 2.4.2: Cleaning of the Zeta Cell or Cuvette 2.4.3: Equipment 2.4.4: Sample Preparation 2.4.5: Colored and Fluorescent Samples 2.4.6: Using Buffers with Metallic Ions 2.4.7: Measuring the ZP in a Cell Culture Medium 2.5: Effect of the ZP on Targeting 2.6 Conclusion Chapter 3: Stability of Targeted Nanoparticles 3.1: Introduction 3.2: Significance of Stability Assessment 3.3: Physical Stability 3.3.1: Particle Size and Size Distribution 3.3.2: Structure and Morphology 3.3.3: Surface Chemistry and Surface Charge 3.3.4: Particle Growth via Aggregation or Agglomeration 3.3.5: Reconstitution Properties 3.4: Chemical Stability 3.4.1: Amount of Drug and Degradation 3.4.2: Drug Release 3.4.3: Drug Leakage 3.4.4: Light Stability 3.4.5: Biological Activity 3.5: Conclusions Chapter 4: Impact of PEGylation on Targeted Nanoparticulate Delivery 4.1: Introduction 4.2: Passive Targeting 4.3: Active Targeting 4.4: Brain Targeting 4.5: Tumor Targeting Chapter 5: Ligands and Receptors for Targeted Delivery of Nanoparticles: Recent Updates and Challenges 5.1: Introduction 5.2: Approaches to Targeted Drug Delivery 5.2.1: Passive Targeting 5.2.2: Active Targeting 5.3: Receptors for Targeted Drug Delivery and Challenges 5.3.1: Receptor-Specific Challenges 5.3.1.1: Identification of receptors 5.3.1.2: Expression characteristics of receptors 5.3.1.3: Receptor accessibility 5.3.1.4: Cellular uptake of receptors 5.4: Ligand-Based Targeted Drug Delivery: Opportunities and Challenges 5.4.1: Selection of Ligand 5.4.2: Ligand Size 5.4.3: Conjugation of a Targeting Ligand with a Drug/Nanocarrier 5.4.4: Ligand Immunogenicity 5.5: Types and in vivo Fate of Targeted Nanoparticles 5.6: Future Prospects and Conclusion Chapter 6: Characterization of Biological Molecule–Loaded Nanostructures Using Circular Dichroism and Fourier Transform Infrared Spectroscopy 6.1: Introduction 6.2: Circular Dichroism 6.2.1: Sample Preparation and Measurement 6.2.2: Drug-Loaded Nanoparticle Characterization by CD 6.3: Fourier Transform Infrared Spectroscopy 6.3.1: Sample Preparation and Measurement 6.3.2: Application of FTIR Spectroscopy for Drug-Loaded Nanoparticle Characterization 6.4: Conclusion Chapter 7: Evaluation of Stimuli-Sensitive Nanoparticles in vitro 7.1: Introduction 7.2: Stimuli-Responsive Nanocarriers 7.3: Stimuli-Responsive Drug Release 7.3.1: Internal Stimuli 7.3.1.1: pH stimuli 7.3.1.2: Redox stimuli 7.3.1.3: Enzyme stimuli 7.3.2: External Stimuli 7.3.2.1: Light stimuli 7.3.2.2: Ultrasound stimuli 7.3.2.3: Thermal stimuli 7.3.2.4: Magnetic stimuli 7.3.3: Multistimulation 7.4: Evaluation of Stimuli Response in Cell Culture 7.4.1: Endolysosomal Escape 7.4.2: Cytotoxicity 7.5: Conclusion Chapter 8: Analytical Techniques for Characterization of Nanodrugs 8.1: Introduction 8.2: Analytical Characterization of Nanodrugs 8.2.1: Drug Encapsulation and Loading Capacity 8.2.1.1: Drug-loading content and drug-loading efficiency 8.2.1.2: Drug entrapment/incorporation efficiency 8.2.2: Techniques for Chemical Composition of Nanodrugs 8.2.2.1: Chromatographic techniques 8.2.2.2: Spectroscopic techniques 8.2.2.3: Calorimetric techniques 8.2.3: Purification Techniques of Nanodrugs 8.2.3.1: Filtration 8.2.3.2: Centrifugation 8.2.3.3: Dialysis 8.2.3.4: Diafiltration 8.2.3.5: Size-exclusion chromatography 8.2.3.6: Electrophoresis 8.3: Physicochemical Characterization of Nanodrugs 8.3.1: Size and Surface Morphology 8.3.1.1: Dynamic light scattering 8.3.1.2: Microscopic techniques 8.3.2: Surface Area 8.3.3: Surface Charge 8.4: In vitro Drug Release Test Methods for Nanodrugs 8.4.1: In vitro Drug Release 8.4.1.1: Sample and separate method 8.4.1.2: Continuous flow method 8.4.1.3: Dialysis membrane methods 8.4.1.4: Combination methods 8.5: Stability of Nanodrugs 8.5.1: Effect of Dosage Form on Stability 8.5.2: Stability Issues Affecting Nanomaterial Properties 8.5.2.1: Changes to particle size and size distribution 8.5.2.2: Changes to particle morphology/shape 8.5.2.3: Self-association 8.5.2.4: Sedimentation/creaming 8.5.2.5: Changes in the surface charge 8.5.2.6: Change in the dissolution/release rate of the active ingredient 8.5.2.7: Drug leakage from a nanomaterial carrier 8.5.2.8: Changes in the chemical composition 8.5.2.9: Interaction with the formulation or container closure 8.5.2.10: Changes in the solid state 8.5.2.11: Changes in microbial stability 8.5.3: Pharmaceutical Stability-Testing Conditions Chapter 9: Cytotoxicity and Biological Compatibility 9.1: Analysis of Cell Viability 9.1.1: Determination of Membrane Disruption as a Measure of Cell Death 9.1.2: Mitochondrial Activity Assessment for Viability Testing 9.1.3: Impedance-Based Viability Assays 9.2: Assays for Cellular Uptake of Nanoparticles 9.3: Drug Delivery Testing through Biological Barriers 9.3.1: In vitro Modeling of the Mucosal Barriers for Drug Delivery 9.3.2: Blood–Brain Barrier Models Chapter 10: Cellular Uptake and Transcytosis 10.1: Introduction 10.2: Cellular Uptake Mechanisms and Nanocarrier Uptake 10.2.1: Cellular Uptake Mechanisms 10.2.1.1: Phagocytosis 10.2.1.2: Pinocytosis 10.2.1.3 Receptor-mediated endocytosis 10.2.2: Cellular Internalization of Nanocarriers 10.2.2.1: Intracellular events 10.3: Effect of Physicochemical Properties of Nanocarriers on Cellular Uptake 10.3.1: Effect of Size and Polydispersity 10.3.2: Effect of Shape 10.3.3: Effect of Surface Charge and Surface Modification 10.3.4: Effect of Hydrophobicity 10.3.5: Effect of Elasticity 10.4: Evaluation of Cellular Uptake Pathways of Nanocarriers in Cell Culture 10.5: Transcytosis of Nanoparticles across Cellular Barriers 10.5.1: Cell Culture Models for Nanoparticle Barrier Permeability 10.5.1.1: Caco-2 cell line 10.5.1.2: HT-29 cell line 10.5.1.3: MDCK cell line 10.5.1.4: T84 cell line 10.5.1.5: 3D cell culture models 10.6 Conclusion Chapter 11: Evaluation of 3D Cell Culture Models for Efficacy Determination of Anticancer Nanotherapeutics 11.1: Introduction 11.2: Types of 3D Cell Culture Models 11.2.1: Scaffold-Based 3D Cell Culture Models 11.2.1.1: Polymeric hard scaffolds 11.2.1.2: Biological scaffolds 11.2.1.3: Micropatterned surface microplates 11.2.2: Scaffold-Free 3D Cell Culture Techniques 11.2.3: Microfluidic 3D Cell Culture 11.3: 3D Cell Culture as a Promising Tool in Anticancer Therapy Development 11.4: Utilization of 3D Cell Culture Models in Evaluationof Nanoparticles 11.5: Conclusion Chapter 12: In vitro and in vivo Blood–Brain Barrier Models for the Evaluation of Drug Transport with Targeted Nanoparticles 12.1: Introduction 12.1.1: The Blood–Brain Barrier 12.1.2: Transport Across the BBB 12.2: In vitro BBB Models 12.2.1: Monocultures 12.2.2: Co-cultures 12.3: In vivo BBB Models 12.4: Conclusion Chapter 13: Sterility Evaluation of Targeted Nanoparticles 13.1: Definitions and the Need for Testing 13.2: Short Review of Methodologies for Sterilization 13.2.1: Removal of Microorganisms 13.2.2: Removal of Endotoxins 13.3: Tests Available to Assess Sterility and Endotoxin Contamination 13.3.1: Cultivation of Fungal and Bacterial Organisms 13.3.2: In vivo and In vitro Endotoxin Testing 13.3.2.1: Rabbit pyrogen test 13.3.2.2: LAL-based assays 13.3.2.3: The rFC assay 13.3.2.4: Alternative assays 13.4: Interference of Nanomaterials in Endotoxin-Testing Systems 13.4.1: Description of Interference of Nanomaterials with in vitro Test Systems 13.4.2: Interference of Nanomaterials with in vitro Endotoxin Testing 13.4.2.1: Optical interference 13.4.2.2: Inhibition/enhancement 13.5: Generic Protocol to Test Interference of Nanomaterials in Endotoxin Tests 13.5.1: Test for Optical Interference 13.5.2: Test for Inhibition/Enhancement 13.6 Summary and Conclusion Chapter 14: Evaluation of Pharmacokinetics and Biodistribution of Targeted Nanoparticles 14.1: Introduction 14.2: Factors Affecting Pharmacokinetics and Biodistribution of Nanoparticles 14.2.1: Blood Circulation and the Reticuloendothelial System 14.2.2: Properties of Nanoparticles 14.2.2.1: Surface properties 14.2.2.2: Size 14.2.2.3: Composition 14.2.2.4: Shape 14.3: Pharmacokinetics of Nanoparticles 14.3.1: Absorption 14.3.2: Distribution 14.3.3: Metabolism 14.3.4: Excretion 14.4: Pharmacokinetic Evaluation of Nanoparticles 14.5: Physiologically Based Pharmacokinetic Modeling for Nanoparticles 14.5.1: PBPK Modeling for the Evaluation of Nanoparticle Biodistribution 14.5.2: PBPK Modeling in the Formulation Development of Nanoparticles 14.6 Conclusion Chapter 15: Evaluation of the in vivo Preclinical Toxicity of Targeted Nanoparticles 15.1: Introduction 15.2: The Effects of Physicochemical Properties of Nanomaterials on Toxicity 15.2.1: Important Exposure Routes 15.2.1.1: The respiratory system 15.2.1.2: Skin 15.2.1.3: The gastrointestinal tract 15.2.2: Nanotoxicity of Nanomaterials and NPs 15.2.2.1: Nanoparticle–DNA interaction 15.2.2.2: Effect on fetuses 15.2.2.3: Toxic effect on the immune system 15.3: Toxicity Studies 15.3.1: Acute Toxicity 15.3.1.1: Acute oral toxicity 15.3.1.2: Acute inhalation toxicity 15.3.1.3: Acute dermal toxicity 15.3.1.4: Acute dermal irritation/corrosion 15.3.2: Subacute Toxicity 15.3.2.1: Subacute oral toxicity 15.3.2.2: Subacute dermal toxicity 15.3.2.3: Subacute inhalation toxicity 15.3.3: Subchronic Toxicity 15.3.3.1: Subchronic oral toxicity 15.3.3.2: Subchronic dermal toxicity 15.3.3.3: Subchronic inhalation toxicity 15.3.4: Chronic Toxicity 15.3.4.1: Chronic toxicity studies 15.3.4.2: Combined chronic toxicity/carcinogenicity studies 15.3.5: Special Toxicities 15.3.5.1: Teratogenicity: prenataldevelopmental toxicity study 15.3.5.2: One-generation reproduction toxicity 15.3.5.3: Two-generation reproductiontoxicity 15.3.5.4: Carcinogenicity studies 15.3.5.5: Immunotoxicity 15.3.5.6: Lymph node proliferation assay Chapter 16: Transdermal Delivery of Targeted Nanoparticles and in vitro Evaluation 16.1: Introduction 16.2: Skin 16.2.1: Structure of the Skin and Barriers 16.2.1.1: Epidermis 16.2.1.2: Dermis 16.2.1.3: Hypodermis 16.2.1.4: Skin appendages 16.2.2: Ways of Drug Delivery through the Skin 16.2.2.1: Intracellular transition 16.2.2.2: Intercellular transition 16.2.2.3: Transition through skin appendages 16.2.3: Factors Affecting Transdermal Drug Delivery 16.2.3.1: Features that depend on the drug active substance 16.2.3.2: Features that depend on the drug delivery systems 16.2.3.3: Physiological properties 16.3: Transdermal Nanocarriers 16.4: Nanoparticles 16.4.1: Preparation Methods of Nanoparticles 16.4.1.1: Emulsion-solvent evaporation 16.4.1.2: Salting out method 16.4.1.3: Emulsions diffusion method 16.4.1.4: Nanoprecipitation 16.4.1.5: Polymerization 16.4.1.6: Dialysis 16.4.1.7: Coacervation or ionic gelation 16.4.1.8: Supercritical fluid technology 16.5: In vitro Studies 16.5.1: In vitro Characterization Studies 16.5.1.1: Size and zeta potential of nanoparticles 16.5.1.2: Drug release profile of nanoparticles 16.5.2: In vitro Cell Studies 16.5.2.1: Skin permeation studies 16.5.2.2: Skin penetration studies 16.6: Therapeutic Application of Transdermal Nanoparticles 16.7: Conclusion Chapter 17: In vivo and in vitro Evaluation of Nose-to-Brain Delivery of Nanoparticles 17.1: Introduction 17.2: Nasal Anatomy and Physiology 17.3: Nose-to-Brain Delivery 17.4: Nasal Delivery Systems 17.4.1: Colloidal Systems in the Aspect of Nasal Delivery 17.4.1.1: Liposomes 17.4.1.2: Cationic liposomes 17.4.1.3: Polymeric micelles 17.4.1.4: Dendrimers 17.4.2: Nanoparticular Systems in the Aspect of Nasal Delivery 17.4.2.1: Solid lipid nanoparticles 17.4.2.2: Polymeric nanoparticles 17.5: Methods for Determining Efficiency of Nose-to-Brain Delivery of Nanoparticles 17.5.1: In vitro Drug Release Methods 17.5.2: In vitro Permeation Studies 17.5.3: In vitro Toxicity Studies 17.5.4: Ex vivo Permeation and Histopathological Studies 17.5.5: In vivo Permeation Studies for Nasal Delivery of Nanoparticles 17.6: Conclusion Chapter 18: Evaluation of Targeted Nanoparticles for Ocular Delivery 18.1: Introduction 18.2: Pharmacokinetic and Bioavailability Studies 18.3: Biodistribution Studies 18.4: Tolerance Assays 18.5: Conclusion Chapter 19: Vaginally Applied Nanocarriers and Their Characterizations 19.1: Introduction 19.2: Novel Approaches for Vaginal Drug Delivery Systems 19.3: Nanotechnology-Based Vaginal System 19.4: Nanosized Dosage Forms Used for Vaginal Drug Delivery 19.4.1: Vesicular systems for Vaginal Drug Delivery 19.4.1.1: Liposomes 19.4.1.2: Niosomes, ethosomes, and transethosomes 19.4.2: Polymeric Nanoparticles 19.4.3: Microemulsions 19.4.4: Dendrimers 19.4.5: Nanofibers 19.4.6: Cyclodextrins 19.5: Conclusion Chapter 20: Oral Administration of Nanoparticles and Approaches for Design, Evaluation, and State of the Art 20.1: Introduction 20.2: Oral Drug Delivery 20.2.1: Gastrointestinal Tract and Related Challenges 20.2.2: Intestinal Absorption 20.3: Nanoparticulate Drug Delivery Systems for Oral Administration 20.3.1: Nanobased Strategies to Overcome the Challenges in Oral Drug Delivery 20.3.1.1: Improving drug solubility 20.3.1.2: Improving stability through the GIT 20.3.1.3: Improving adhesion and diffusion through the GIT 20.4: Oral Administrations of Nanoparticulate Drug Delivery Systems 20.4.1: Cancer Therapy 20.4.2: Protein and Peptide Drugs 20.4.3: Intestinal Targeting 20.4.3.1: Inflammatory bowel disease and colon targeting for colorectal cancer Chapter 21: Drug Resistance Mechanisms and Strategies to Overcome Drug Resistance with Nanoparticulate Systems 21.1: Introduction 21.2: Antimicrobial Resistance 21.2.3: Nanoparticles and AMR 21.2.3.1: Metallic nanoparticles 21.2.3.2: Polymeric nanoparticles 21.2.3.3: Nitric oxide–releasing nanoparticles 21.2.4: In vitro Antimicrobial Activity Methods 21.2.4.1: Disk diffusion 21.2.4.2: Dilution 21.2.4.3: The checkerboard method 21.2.4.3: Time–kill curves 21.2.1: Antibiotic Resistance 21.2.2: Development Mechanism of AMR 21.3: Anticancer Resistance 21.3.1: The Potential Mechanism of Anticancer Drug Resistance 21.3.1.1: Tumor heterogeneity and microenvironment 21.3.1.2: Mitochondria-mediated chemoresistance 21.3.1.3: Epithelial–mesenchymal transition 21.3.1.4: Altering drug targeting 21.3.1.5: Increased drug efflux 21.3.2: Nanoparticles in Overcoming Chemoresistance 21.3.2.1: Targeted drug delivery 21.3.2.2: Delivery of chemosensitizing molecules 21.3.2.3: Subcellular drug delivery 21.3.3: In vitro Chemosensitivity Assay 21.3.3.1: MTT assay 21.3.3.2: Clonogenic assay Chapter 22: Clinical Trials of Targeted Nanoparticulate Drug Delivery Systems 22.1: Introduction 22.2: Clinical Trials of Targeted Nanoparticulate Drug Delivery Systems 22.2.1: MM-302 22.2.2: ThermoDox 22.2.3: BIND-014 22.3: Conclusion Chapter 23: Evaluation of Targeted Mesoporous Silica Nanoparticles 23.1: Synthesis and Manufacturing 23.2: Biocompatibility 23.3: Functionalization 23.4: Targeting 23.4.1: Passive Targeting 23.4.1.1: Size and Shape 23.4.1.2: Surface charge and composition 23.4.2: Active Targeting 23.4.2.1: Antibodies 23.4.2.2: Proteins/peptides 23.4.2.3: Vitamins 23.4.2.4: Saccharides 23.5: Conclusion Chapter 24: Evaluation of Targeted Liposomes 24.1: Introduction 24.2: Classification of Liposomes 24.2.1: Based on Structure and Size 24.2.1.1: Unilamellar vesicles 24.2.1.2: Multilamellar vesicles 24.2.2: Based on the Drug Release Mechanism 24.3: Manufacturing of Liposomes 24.3.1: Composition 24.3.2: Direct Mechanical Agitation/Sonication 24.3.3: Thin-Film Hydration 24.3.4: Solvent Dispersion/Injection 24.3.5: Lyophilization of Liposomes 24.3.6: Sterilization Methods for Liposomes 24.4: Characterization of Liposomes 24.4.1: Size, Size Distribution, and Concentration 24.4.2: Determination of Encapsulated Molecules inside Liposomes 24.4.3: Physicochemical Characterization 24.4.3.1: Determination of lamellarity 24.4.3.2: Transition temperature 24.4.3.3: Surface charge 24.4.3.4: Zeta potential 24.4.4: Surface Morphology and Polymer Modification 24.4.5: Liposome–Drug Interaction 24.4.6: Determination of the Residual Organic Solvent 24.4.7: Regulatory Perspective for Liposome Registration Chapter 25: Prospects of Nanomedicine with Nanocrystal Technology 25.1: Nanonization Techniques and Application Areas 25.2: Nanoparticle Systems 25.2.1: Nanocrystal Definition 25.2.2: Properties of Nanocrystals 25.2.2.1: Increase in dissolution rate by surface area enlargement 25.2.2.2: Increase in saturation solubility 25.2.2.3: Increased adhesion to cell membranes 25.2.3: Production of Nanocrystals 25.2.3.1: Bottom up processes 25.2.3.2: Top-down processes 25.2.3.3: Other techniques for the production of drug nanocrystals 25.2.4: Advantages and Application Areas of Orally Applied Nanocrystalline Formulations Chapter 26: Characteristics of Marketed Nanopharmaceutics 26.1: Different Types of Nanocarriers and Their Main Advantages 26.2: From Laboratory to Market 26.3: Approved Nonopharmaceutics and Their Features 26.3.1: Liposomal-Based Nanopharmaceutics 26.3.1.1: Liposomal-based nanodrugs approved for anticancer treatment 26.3.1.2: Liposomal nanodrugs approved for antifungal treatment 26.3.1.3: Liposome-based drugs approved for analgesic treatment 26.3.1.4: Liposome-based drug approved for neovascularization treatment 26.3.1.5: Lipid-based drug approved for hereditary transthyretin-mediated amyloidosis treatment 26.3.2: Polymer-Based Nanopharmaceutics 26.3.3: Protein-Based Nanopharmaceutics 26.3.4: Micelle-Based Nanopharmaceutics 26.3.5: Crystalline-Based Nanopharmaceutics 26.3.6: Inorganic/Metallic Nanopharmaceutics 26.4: Nanopharmaceutical Market Size 26.5: Future Perspective Chapter 27: Regulatory Guidelines of the US Food and Drug Administration and the European Medicines Agency for Actively Targeted Nanomedicines 27.1: Introduction 27.2: The European Medicines Agency’s Scientific Guidelines for Actively Targeted Nanomedicines 27.2.1: Reflection Paper on Surface Coatings: General Issues for Consideration Regarding Parenteral Administration of Coated Nanomedicine Products 27.2.2: Data Requirements for Intravenous Liposomal Products Developed with Reference to an Innovator Liposomal Product 27.2.3: Development of Block-Copolymer-Micelle Medicinal Products 27.2.4: Data Requirements for Intravenous Iron-Based Nanocolloidal Products Developed with Reference to an Innovator Medicinal Product 27.3: The Food and Drug Administration’s Scientific Guidelines for Actively Targeted Nanomedicines 27.3.1: Considering whether an FDA-Regulated Product Involves the Application of Nanotechnology 27.3.2: Drug Products, Including Biological Products, That Contain Nanomaterials 27.3.2.1: Quality: chemistry, manufacturing, and controls 27.3.2.2: Nonclinical studies 27.3.2.3: Clinical development 27.3.3: Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation 27.3.3.1: Chemistry, manufacturing, and controls 27.3.3.2: Human pharmacokinetics: Bioavailability and bioequivalence 27.3.3.3: Labeling 27.4: Conclusion Index