Biomaterial-Inspired Nanomedicines for Targeted Therapies

Preface
Acknowledgments
Contents
Editors and Contributors
About the Editors
Contributors
1: Introduction to Biomaterial-Inspired Nanomedicines
	1.1	 Introduction
	1.2	 Ideal Property of Nanomaterials
	1.3	 Nanostructured Biomaterials
	1.4	 Host-Nanobiomaterial Interactions
	1.5	 Classification of Nanomaterials
		1.5.1	 Based on Dimension
		1.5.2	 Based on Nanostructures
		1.5.3	 Based on Composition
	1.6	 Synthesis of Nanomaterials
	1.7	 Characteristics of Nanomaterials
	1.8	 Biomedical Application of Nanomaterials
		1.8.1	 Diagnosis
		1.8.2	 Drug Delivery and Therapeutic Targeting
			1.8.2.1	 Passive Targeting
			1.8.2.2	 Active Targeting
			1.8.2.3	 Stimuli-Responsive Targeting
		1.8.3	 Theragnostic
	1.9	 Challenges to the Translation of Nanobiomaterials
		1.9.1	 Toxicity Concern
		1.9.2	 Regulatory Considerations
		1.9.3	 Commercialization
	1.10	 Conclusion
	References
2: Exploring the Potential of Nano-Biomaterials in Tissue Engineering
	2.1	 Introduction
	2.2	 Brief Background of Nano-Biomaterial for Tissue Engineering Applications
	2.3	 Desired Characteristics of Nano-Biomaterial for Tissue Engineering
		2.3.1	 Biocompatibility
		2.3.2	 Biodegradability
		2.3.3	 Mechanical Properties
		2.3.4	 Porosity
		2.3.5	 Tunable Properties
		2.3.6	 Topography
	2.4	 Emerging Strategies Employing Nano-Biomaterial for Tissue Engineering
		2.4.1	 3D Bioprinting
		2.4.2	 Stem Cell-Based Nano-Biomaterials
		2.4.3	 Nanogel
		2.4.4	 Nanoparticles
		2.4.5	 Nanofiber
		2.4.6	 Nano-Bioglass
		2.4.7	 Carbon-Based Nanomaterials (CNMs)
	2.5	 Application of Nano-Biomaterial in Tissue Engineering
		2.5.1	 Skin Tissue Engineering
		2.5.2	 Bone Tissue Engineering
		2.5.3	 Cartilage Tissue Engineering
		2.5.4	 Cardiac Tissue Engineering
		2.5.5	 Neural Tissue Engineering
		2.5.6	 Retinal Tissue Engineering
		2.5.7	 Dental and Periodontal Tissue Engineering
	2.6	 Clinical Translation and Regulatory Hurdles
	2.7	 Conclusion and Future Perspective
	References
3: Targeting the Blood-Brain Barrier with Nano-Biomaterials
	3.1	 Introduction
	3.2	 Physiology of BBB
		3.2.1	 Brain Endothelial Cells (BECs)
		3.2.2	 Endothelial Cell TJ
		3.2.3	 Pericytes
		3.2.4	 Immune Cells
		3.2.5	 Astrocytes (ACs)
		3.2.6	 Basement Membrane (BM)
	3.3	 Transport Across BBB Per Se and Through Nanotechnology
		3.3.1	 Passive Diffusion: Paracellular/Transcellular
		3.3.2	 Carrier-Mediated Transport (CMT)/Solute Carrier Transport
		3.3.3	 Receptor-Mediated Transport (RMT)
		3.3.4	 Adsorptive-Mediated Transport (AMT)
		3.3.5	 Cell-Mediated Transport (CMT)
	3.4	 Nano-Biomaterials for BBB Targeting
		3.4.1	 Organic NPs
			3.4.1.1	 Liposomes
			3.4.1.2	 Solid Lipid Nanoparticles (SLNPs)
		3.4.2	 Polymeric NPs
			3.4.2.1	 Poly (Butyl Cyanoacrylate) (PBCA)
			3.4.2.2	 Poly (Lactic-Co-Glycolic Acid) (PLGA)
			3.4.2.3	 Chitosan (CS)
		3.4.3	 Inorganic NPs
			3.4.3.1	 Fullerene
			3.4.3.2	 Graphene
			3.4.3.3	 Carbon Nanotubes (CNTs)
			3.4.3.4	 Quantum Dots
			3.4.3.5	 Metal NPs
	3.5	 Toxicity of Nano-Biomaterials
	3.6	 Conclusion
	References
4: Nano-Vaccines: Opportunities and Challenges in Biomaterial-Based Vaccine Delivery
	4.1	 Introduction
	4.2	 Biomaterials in Vaccine Delivery
		4.2.1	 Nanoparticles as Vaccine Carriers
		4.2.2	 Lipid-Based Nanoparticles
		4.2.3	 Polymer-Based Nanoparticles
		4.2.4	 Liposomes, Micelles, and Other Nanostructures
	4.3	 Antigen Encapsulation and Presentation
	4.4	 Targeted Vaccine Delivery
	4.5	 Enhanced Immune Response, Safety, and Efficacy
	4.6	 Conclusion and Future Challenges
	References
5: Approaches to the Treatment of Pulmonary Obstruction: The Role of Nano-Biomaterials in Therapeutic Targeting
	5.1	 Introduction
	5.2	 Types
		5.2.1	 Pulmonary Embolism
		5.2.2	 Pulmonary Artery Stenosis
		5.2.3	 Pulmonary Hypertension
		5.2.4	 Bronchial Obstruction
	5.3	 Causes
	5.4	 Clinical Symptoms
		5.4.1	 Pulmonary Embolism
		5.4.2	 Pulmonary Artery Stenosis
		5.4.3	 Pulmonary Hypertension
		5.4.4	 Bronchial Obstruction
	5.5	 Diagnosis
		5.5.1	 Medical History and Physical Examination
		5.5.2	 Imaging Studies
		5.5.3	 Positron Emission Tomography (PET)
		5.5.4	 Pulmonary Function Tests (PFTs)
		5.5.5	 Blood Tests
		5.5.6	 Echocardiogram
		5.5.7	 Angiography
		5.5.8	 Bronchoscopy
	5.6	 Current Treatment Approaches
		5.6.1	 Medications and Inhalers
			5.6.1.1	 Medications for Pulmonary Obstruction
			5.6.1.2	 Inhalers and Their Importance
		5.6.2	 Limitations of Existing Treatments
	5.7	 The Role of Nano-Biomaterials in Inhaler Technology
		5.7.1	 Key Properties and Advantages
		5.7.2	 Imaging and Diagnostic Applications
		5.7.3	 Therapeutic Applications
	5.8	 Drug Delivery in Pulmonary Obstruction
		5.8.1	 Challenges in Drug Delivery
		5.8.2	 Advancements in Drug Delivery
		5.8.3	 Safety Concern
	5.9	 Clinical Considerations
	5.10	 Conclusion
	References
6: Targeting of Tumor Microenvironment Through Nano-Biomaterial-Based Chemotherapy
	6.1	 Introduction
	6.2	 Key Challenges in Efficient Chemotherapy and Complexity of Tumor Microenvironment (TME)
		6.2.1	 Challenges Posed by Cancer or Tumor Cells
			6.2.1.1	 Tumor Microenvironment
			6.2.1.2	 Tumor Heterogeneity
			6.2.1.3	 Tumor Dormancy
			6.2.1.4	 Tumor Hypoxia
			6.2.1.5	 Cancer Stem Cells
			6.2.1.6	 Drug Resistance
			6.2.1.7	 Tumor Metastasis
			6.2.1.8	 Tumor Evading Action
				Ability to Evade the Immune System
				Ability to Evade Anti-Angiogenic Therapies
			6.2.1.9	 Physiological Barriers
			6.2.1.10	 Multidrug Resistance
	6.3	 Approaches to the Targeting of Cancer
		6.3.1	 Active and Passive Targeting
		6.3.2	 Targeting by Gene Silencing
		6.3.3	 Drug Delivery Approaches
		6.3.4	 NPs-Based Hyperthermia
		6.3.5	 Radiotherapy Via NPs
	6.4	 NPs in the Treatment of Cancer
	6.5	 Nano-Oncoimmunotherapies and Their Link to Existing Immunotherapies
		6.5.1	 Targeting of Small Therapeutic Molecules to TME
		6.5.2	 Vaccines and Antigen-Based NP for OIMTs
		6.5.3	 Gene-Based OIMTs
	6.6	 Safety Concern
	6.7	 Conclusion
	References
7: Harnessing the Targeting Potential of Nano-biomaterials to Treat Autoimmune Skin Disorders
	7.1	 Introduction
	7.2	 Autoimmune Skin Disorders
	7.3	 Origins of Autoimmune Skin Diseases
	7.4	 Challenges in Drug Delivery Through Skin and Strategies to Overcome
	7.5	 Application of Nano-biomaterials for Targeting Autoimmune Skin Diseases
		7.5.1	 Lipid Nanoparticles
		7.5.2	 Polymeric Nanoparticles
		7.5.3	 Nanoemulsions
		7.5.4	 Nanomicelles
		7.5.5	 Gold Nanoparticles
		7.5.6	 Mesoporous Silica Nanoparticles
		7.5.7	 Iron Oxide Nanoparticles
		7.5.8	 Silver Nanoparticles (AgNPs)
	7.6	 Conclusion
	References
8: Biomaterials in the Design of Nanosensors for Disease Diagnosis
	8.1	 Introduction
	8.2	 Classification of Sensors
		8.2.1	 Chemical Nanosensors
		8.2.2	 Deployable Nanosensors
		8.2.3	 Electrometers
		8.2.4	 Biosensors
		8.2.5	 Biosensors-on-Chip
		8.2.6	 Optical Nanosensors
		8.2.7	 Fiber Optic Nanosensors
		8.2.8	 Electromagnetic Nanosensors
		8.2.9	 Electrical Current Measurement
		8.2.10	 Magnetic Nanosensors
		8.2.11	 Mechanical Nanosensors
	8.3	 Types of Nanosensors
		8.3.1	 Nanosensors Based on Nanoparticles and Nanoclusters
		8.3.2	 Nanosensors Based on Carbon Nanotubes (CNTs)
		8.3.3	 Nanosensors Based on Graphene
		8.3.4	 Nanosensors Based on Bulk Nanostructured Materials
		8.3.5	 Nanosensors Based on Metal-Organic Frameworks (MOFs)
	8.4	 Invention and General Development Procedure of Nanosensors
	8.5	 Applications of Nanosensors in Disease Diagnosis
		8.5.1	 In the Early Diagnosis of Cancer
		8.5.2	 Cancer Detection
		8.5.3	 Lung Cancer
		8.5.4	 Breast Cancer
		8.5.5	 Colorectal Cancer
		8.5.6	 Progressive Neurological Diseases
	8.6	 Drug Delivery
	8.7	 Nanomaterials Applied for Nanosensors
		8.7.1	 Metal and Noble Metals Nanomaterials
		8.7.2	 Metal Oxide Nanoparticles
		8.7.3	 Carbon-Based Nanomaterials
	8.8	 Polymer and Bio-nanomaterials
	8.9	 Conclusions and Future Directions
	References
9: Nano-biomaterials: A Site-Targeted Approach to Antidiabetic Drug Delivery
	9.1	 Introduction
		9.1.1	 Background and Significance
		9.1.2	 Objectives of the Study
	9.2	 Nano-biomaterials in Drug Delivery
		9.2.1	 Overview of Drug Delivery Systems
		9.2.2	 The Role of Nanotechnology in Drug Delivery
		9.2.3	 Benefits of Nano-biomaterials in Antidiabetic Drug Delivery
	9.3	 Antidiabetic Drug Delivery Challenges
		9.3.1	 Current Limitations in Antidiabetic Drug Delivery
		9.3.2	 Targeted Drug Delivery as a Solution
	9.4	 Nanocarrier Strategies for Enhanced Delivery of Antidiabetic Agents
		9.4.1	 Nanoparticles
			9.4.1.1	 Synthetic Polymers-Based NPs
			9.4.1.2	 Natural Polymers-Based NPs
			9.4.1.3	 Combination of Natural and Synthetic Polymers-Based NPs
		9.4.2	 Lipid-Based Drug Delivery Systems
			9.4.2.1	 Solid Lipid Nanoparticles (SLNs)
			9.4.2.2	 Nanostructured Lipid Carriers (NLCs)
			9.4.2.3	 Micro and Nano-emulsions
			9.4.2.4	 Self-emulsifying Drug Delivery Systems (SEDDS)
		9.4.3	 Vesicular Systems
			9.4.3.1	 Liposomes
			9.4.3.2	 Niosomes
			9.4.3.3	 Ethosomes
			9.4.3.4	 Virosomes
			9.4.3.5	 Aquasomes
			9.4.3.6	 Cubosomes
			9.4.3.7	 Dendrimers
			9.4.3.8	 Polymeric Micelles
		9.4.4	 Gene Therapy
	9.5	 Nano-biomaterials in Preclinical Studies
	9.6	 Clinical Applications
	9.7	 Patented Technologies for Antidiabetic Drug Delivery
	9.8	 Challenges and Future Directions
	9.9	 Conclusion
	References
10: Nanobiomaterials in the Management of Wound Healing
	10.1	 Introduction
	10.2	 Drawbacks of Current Remedy and the Necessity of Biomaterials in Wound Healing
	10.3	 Standalone Biomaterials
	10.4	 Biomaterials Encapsulating Bioactive
	10.5	 Biomaterials Encapsulating Cell Remedies
	10.6	 Requirements of Nanomaterials for Effective Delivery in Wound Healing
	10.7	 Different Nanobiomaterials for Effective Wound Healing
		10.7.1	 Liposomes
		10.7.2	 Micelles
		10.7.3	 Nanogels
		10.7.4	 Polymeric Nanoparticles
		10.7.5	 Solid Lipid Nanoparticles
		10.7.6	 Inorganic Nanoparticles
		10.7.7	 Nanofibers
		10.7.8	 Clinical Uses of Nanobiomaterials
	10.8	 Conclusions
	References
11: Nano-Biomaterial-Assisted Targeted Therapy of Central Nervous System Disorders
	11.1	 Introduction
	11.2	 Hurdles to CNS Delivery
		11.2.1	 Blood–Brain Barrier
		11.2.2	 Blood–Cerebrospinal Fluid Barrier (B–CSF)
	11.3	 Importance of Nano-Biomaterials Targeting in CNS Delivery
	11.4	 Applications of Nano-Biomaterials in Targeted CNS Delivery
		11.4.1	 Lipidic Nano-Biomaterials
		11.4.2	 Polymeric Nano-Biomaterials
		11.4.3	 Inorganic Nano-Biomaterials
		11.4.4	 Carbon-Based Nano-Biomaterials
		11.4.5	 Dendrimers
	11.5	 Regulatory Hurdles Towards Clinical Translation
	11.6	 Conclusion and Future Outlook
	References
12: Therapeutic Applications of Nanobiomaterials for the Management of Ocular Diseases
	12.1	 Introduction
	12.2	 Anatomy of an Eye
		12.2.1	 Anterior Segment
			12.2.1.1	 Tear Film
			12.2.1.2	 Cornea
			12.2.1.3	 Conjunctiva
			12.2.1.4	 Iris, Ciliary Body, and Lens
		12.2.2	 Posterior Segment
			12.2.2.1	 Sclera
			12.2.2.2	 Choroid
			12.2.2.3	 Retina
			12.2.2.4	 Vitreous Body
	12.3	 Nanobiomaterials for the Treatment of Ocular Diseases
		12.3.1	 Age-Related Macular Degeneration
		12.3.2	 Diabetic Retinopathy
		12.3.3	 Conjunctivitis
		12.3.4	 Keratitis
		12.3.5	 Glaucoma
	12.4	 Drug Delivery Devices for Ocular Nanobiomaterial Delivery
		12.4.1	 Microneedles
		12.4.2	 Contact Lens
	12.5	 Conclusion
	References
13: Nanoparticle-Based Drug Delivery for Infectious Diseases
	13.1	 Introduction
	13.2	 Development of Nanoparticle-Based LA Formulations for Chronic Diseases
		13.2.1	 HIV
			13.2.1.1	 The Need for Consistent Antiretroviral Medication for HIV
			13.2.1.2	 Nanocrystal-Based Delivery Systems for LA ART
		13.2.2	 Viral Hepatitis
			13.2.2.1	 Current Treatment Approach
			13.2.2.2	 The Potential of Nanomedicine in Meeting the Unmet Need for LA Medicines for HBV
		13.2.3	 Tuberculosis
			13.2.3.1	 Current Treatment Approaches
			13.2.3.2	 TB Transmissibility and Pathogenesis
			13.2.3.3	 Anti-TB Drugs and Suitability for LA Nanoparticle Formulation
		13.2.4	 Malaria
			13.2.4.1	 Current Treatment Approaches
			13.2.4.2	 Long-Acting Nanomedicine as Chemoprophylaxis for Malaria
	13.3	 Conclusion and Future Direction
	References
14: Stimuli-Responsive Drug Delivery System: Current Application in Osteoarticular Diseases and Future Directions
	14.1	 Introduction
	14.2	 Stimuli-Responsive Nano-drug Delivery Systems for Osteoarticular Diseases
		14.2.1	 ROS-Responsive Nano-drug Delivery Systems
		14.2.2	 PH-Responsive Nano-drug Delivery Systems
		14.2.3	 Enzyme-Responsive Nano-drug Delivery Systems
		14.2.4	 External Stimuli-Responsive Nano-drug Delivery Systems
	14.3	 The Application of Stimuli-Responsive Drug Delivery System in Multiple Osteoarticular Diseases
		14.3.1	 RA
		14.3.2	 OA
		14.3.3	 Bone Defect
	14.4	 Conclusion and Future Perspective
	References
15: Nano-biomaterial Mediated Delivery of Therapeutic Agents for the Treatment of Gastrointestinal Diseases
	15.1	 Introduction
	15.2	 Nanogels
		15.2.1	 Synthesis of Nanogels
			15.2.1.1	 Self-Assembly Through Physical Interaction
			15.2.1.2	 Chemical Crosslinking
			15.2.1.3	 Emulsion Polymerization
			15.2.1.4	 Template-Assisted Fabrication
		15.2.2	 Nanogels for Antimicrobial Delivery
		15.2.3	 Nanogels for Anticancer Drug Delivery
		15.2.4	 Nanogels for Antidiabetic Drug Delivery
	15.3	 Liposomes
		15.3.1	 Preparation of Liposomes or Nanoliposomes
			15.3.1.1	 Thin-Film Hydration Method (Bangham Method)
			15.3.1.2	 Detergent Removal (Depletion) Method
			15.3.1.3	 Solvent Injection Method
			15.3.1.4	 Downsizing and Post-formation Processing
		15.3.2	 Nanoliposomes for Antimicrobial Drug Delivery
		15.3.3	 Nanoliposomes for Antidiabetic Drug Delivery
		15.3.4	 Nanoliposomes for Anticancer Delivery
	15.4	 Micelles
		15.4.1	 Preparation of Micelles
			15.4.1.1	 Direct Dissolution
			15.4.1.2	 Dialysis
			15.4.1.3	 Oil-in-Water Emulsion Evaporation
			15.4.1.4	 Co-solvent Evaporation
			15.4.1.5	 Microphase Separation
		15.4.2	 Micelles for Antimicrobial Drug Delivery
		15.4.3	 Micelles for Antidiabetic Drug Delivery
		15.4.4	 Micelles for Anticancer Drug Delivery
	15.5	 Nanoparticles
		15.5.1	 Synthesis of Nanoparticles
			15.5.1.1	 Desolvation and Self-Assembly Method
			15.5.1.2	 Emulsification Method
			15.5.1.3	 Nanospray Drying Method and Electrospray Method
			15.5.1.4	 Complex Coacervation Method
			15.5.1.5	 Ionic Gelation Method
		15.5.2	 Nanoparticles for Antimicrobial Delivery
		15.5.3	 Nanoparticles for Anticancer Delivery
		15.5.4	 Nanoparticles in Antidiabetic Drug Delivery
	15.6	 Conclusion and Future Perspectives
	References
16: Advances in Nano-biomaterials for Effective Antimicrobial Therapy
	16.1	 Introduction
	16.2	 Antibiotic Resistance and Nano-materials
	16.3	 Synergistic Antimicrobial Activity of Nanoparticles
	16.4	 Classification of Antimicrobial Nano-biomaterials
		16.4.1	 Macroscale Biomaterials
			16.4.1.1	 Antimicrobial Peptides
			16.4.1.2	 Polymeric Biomaterials
		16.4.2	 Nanoscale Biomaterials or Nano-materials
			16.4.2.1	 One-Dimensional Nano-materials
			16.4.2.2	 Two-Dimensional Nanostructures
	16.5	 Nanoparticles with Antimicrobial Therapy and Mode of Action
		16.5.1	 Silver Nanoparticles
		16.5.2	 Zinc Oxide Nanoparticles
		16.5.3	 Titanium Dioxide Nanoparticles
		16.5.4	 Gold Nanoparticles
		16.5.5	 Copper and Aluminum Nanoparticles
		16.5.6	 Chitosan and Antimicrobial Peptides
		16.5.7	 Fullerenes and Fullerene Derivatives
		16.5.8	 Carbon Nanotubes (CNT)
		16.5.9	 Nanoparticles Capable of Releasing Nitric Oxide
		16.5.10	 Surfactants Based on Nanoemulsions
	16.6	 Development of Antibacterial-Biofilm with Magnetic Nanoparticles
		16.6.1	 Visualization of Biofilm Architecture
	16.7	 Advances in Antimicrobial Peptide-Based Biomaterials for Bacterial Infections
	16.8	 Mechanism of Action of Nanoparticles and Future Perspective
	16.9	 Challenges of Nanoparticles for Antimicrobial Therapy
	16.10	 Conclusion
	References
17: Clinical and Regulatory Consideration for Nanobiomaterials
	17.1	 Introduction
	17.2	 Outline of Drug Development
	17.3	 Culmination of Nanobiomaterials for Drug Delivery
	17.4	 Properties of Nanobiomaterials
	17.5	 Inherent Difficulties in Regulation of Nanobiomaterials
	17.6	 Clinical Status of Nanobiomaterials in Drug Delivery
	17.7	 Nanobiomaterial Regulatory Strategies on a Global Scale
		17.7.1	 USA
		17.7.2	 United Kingdom (UK)
		17.7.3	 European Commission (EU)
		17.7.4	 India
		17.7.5	 Canada
		17.7.6	 Japan
		17.7.7	 Others
	17.8	 Conclusion
	References