Macrophage Targeted Delivery Systems: Basic Concepts and Therapeutic Applications

Foreword
Preface
Contents
Contributors
Part I: Anatomy, Physiology and Pharmacology of Macrophages
	Introduction to Pharmacology of Macrophages with Drug Delivery Perspective
		1	 Introduction
		2	 What Is a Macrophage?
			2.1	 Macrophage Origin
		3	 Activation States of Macrophages
			3.1	 Classical Activation
			3.2	 Innate Activation
			3.3	 Alternative Activation
			3.4	 Deactivation
		4	 Types of Macrophages
			4.1	 Kupffer Cells
			4.2	 Splenic Macrophages
			4.3	 Dendritic Cells
			4.4	 Macrophages/Dendritic Cells of the Skin
			4.5	 Macrophages and Dendritic Cells of the Gut/Intestine
		5	 Recognition and Destruction by Macrophages and Subversion by Pathogens
		6	 Drug Delivery to Macrophages
			6.1	 Active and Passive Targeting of Macrophages
			6.2	 Parasitic Infectious Diseases
			6.3	 Viral Infectious Disease: AIDS Therapy
			6.4	 Inflammatory Diseases
				6.4.1	 Atherosclerosis and Restenosis
				6.4.2	 Rheumatoid Arthritis
			6.5	 Neuroinflammatory Diseases
		7	 Conclusion
		References
	Introduction to Anatomy and Physiology of Macrophages from Drug Delivery Perspective
		1	 Introduction
		2	 Anatomy and Physiology of Macrophages
			2.1	 Origin of Tissue Macrophages
			2.2	 M1 and M2 Phenotypes of Macrophages
			2.3	 Macrophages in Development
				2.3.1	 Macrophages in Erythropoiesis
				2.3.2	 Macrophages in Brain Development
				2.3.3	 Macrophages in Lung Homeostasis
			2.4	 Macrophages in Metabolism
				2.4.1	 Macrophages in Metabolic Syndrome
				2.4.2	 Macrophages and Iron Recycling
		3	 Macrophages as a Target for Drug Delivery
			3.1	 Targeting Macrophage for Intracellular Pathogen Therapy
			3.2	 Targeting Macrophage for Therapy in HIV-1 Infection
			3.3	 Targeting Macrophages for Rheumatoid Arthritis (RA)
			3.4	 Targeting Macrophages for Cancer
				3.4.1	 Tumor-Associated Macrophages in Cancer Development
				3.4.2	 Origins of Tumor-Associated Macrophages (TAMs)
				3.4.3	 Therapeutic Approaches for Cancer
		References
	Mechanisms and Ways of Macrophage Delivery
		1	 Introduction
		2	 Differentiation into Macrophages
		3	 Signaling Pathways
		4	 Pathways Affecting the Polarization of Macrophages
		5	 Inflammatory Reactions
		6	 Phagocytosis
		7	 Non-opsonic Receptors
		8	 Opsonic Receptors
		9	 Apoptotic Cells
		10	 Phagosome Signaling
		11	 Phagosome Maturation
		12	 Drug Delivery
		13	 Conclusion
		14	 Future Trends
		References
	Macrophage-Associated Disorders: Pathophysiology, Treatment Challenges, and Possible Solutions
		1	 Introduction
			1.1	 Polarization of MPs
				1.1.1	 Pro-inflammatory M1 Macrophages
				1.1.2	 Anti-inflammatory M2 Macrophages
			1.2	 Macrophage Function
		2	 Role of MPs in Disease Pathogenesis
			2.1	 Role of MPs in the Pathogenesis of Acute/Chronic Inflammation
				2.1.1	 Type 1 Diabetes (TD1)
				2.1.2	 Inflammatory Bowel Disease (IBD)
				2.1.3	 Rheumatoid Arthritis (RA)
				2.1.4	 Systemic Lupus Erythematosus (SLE) Treatment
				2.1.5	 Multiple Sclerosis (MS)
			2.2	 Role of MPs in the Pathogenesis of Cardiovascular Disease (CVD)
				2.2.1	 Myocardial Fibrosis (MF)
				2.2.2	 Myocardial Infarction (MI)
			2.3	 Role of MPs in the Pathogenesis of Cancer
				2.3.1	 MPs and Tumor Cell Activation
				2.3.2	 MPs and Immunosuppression
				2.3.3	 MPs and Angiogenesis
				2.3.4	 MPs and Tumor Invasion and Metastasis
		3	 Treatment Challenges in MP-Based Therapy
			3.1	 Status Quo of MPs
			3.2	 Imperative Concerns for Preclinical Models
			3.3	 Issues Regarding Quality Control
			3.4	 Miscellaneous Concerns
		4	 Treatment Approaches as Promising Solution for Dealing with MPs Associated Disorders
			4.1	 Targeting MPs for Acute/Chronic Inflammation
				4.1.1	 Type 1 Diabetes (TD1) Treatment
				4.1.2	 Inflammatory Bowel Disease (IBD) Treatment
				4.1.3	 Rheumatoid Arthritis (RA) Treatment
				4.1.4	 Systemic Lupus Erythematosus (SLE) Treatment
				4.1.5	 Multiple Sclerosis (MS) Treatments
			4.2	 MPs Targeting for Treating Cardiovascular Disease (CVD)
				4.2.1	 Myocardial Fibrosis (MF) Treatment
				4.2.2	 Treatment of Myocardial Infarction (MI)
			4.3	 Targeting MPs for Cancer Therapy
				4.3.1	 MPs Targeting to Aim STs
					Stalling Monocyte Infiltration
					Repolarizing TAMs
					Depleting TAMs
		5	 Nanomedicine: A Novel Approach to Deal with Cancer as a Prototype of MPs Targeting
			5.1	 MPs Captured Nanomedicines: New Live Cell-Intervened Drug Delivery Systems (LCDDS) for Cancer Therapy
			5.2	 Nanoparticles for MPs Imaging: For Prognosis and Identification of Cancer
		6	 Future Prospects
		Acronyms
		References
	Understanding Macrophage-Associated Diseases and Applications of Nanodrug Delivery Systems
		1	 Introduction
		2	 Understanding Macrophages Role in Disease Pathology
			2.1	 Atherosclerosis
			2.2	 Asthma
			2.3	 Obesity and Diabetes
			2.4	 Cancer
			2.5	 Chronic Wound
			2.6	 Rheumatoid Arthritis
			2.7	 Neurodegenerative Diseases
		3	 Targeting Macrophages by Nanodrug Delivery System
		4	 Targeting Cancer
			4.1	 Targeting Tumor-Associated Macrophages
				4.1.1	 Inhibition of TAMs Recruitment
				4.1.2	 Directly Killing Tumor TAMs
				4.1.3	 Reeducate Tumor TAMs
		5	 Arthritis
		6	 Obesity and Diabetes
		7	 Inflammatory Diseases
		8	 Major Challenges in Macrophages Targeting
			8.1	 Nanomedicines Loaded in Macrophages
		9	 Conclusion
		Bibliography
Part II: Polymeric Nanoparticles for Macrophage Targeting
	Polymeric Nanoparticles-Assisted Macrophage Targeting: Basic Concepts and Therapeutic Goals
		1	 Introduction
		2	 Role of Macrophages in Various Diseases Inflammation
			2.1	 Role of Macrophages in Cancer
			2.2	 Role of Macrophages in Metabolic Homeostasis
			2.3	 Role of Macrophages in Liver Diseases
		3	 Various Receptors Overexpressed in Macrophages During Inflammation
			3.1	 Activin
			3.2	 Toll-Like Receptors
			3.3	 CD44 Receptor
			3.4	 G Protein-Coupled Receptors (GPCRs)
			3.5	 Mannose Receptor
		4	 Polymeric Nanoparticles
			4.1	 Formulation of Polymeric Nanoparticles
		5	 Polymeric Nanoparticles Assisted Macrophage Targeting
			5.1	 Passive Targeting of Macrophages
			5.2	 Active Targeting of Macrophages
				5.2.1	 Hyaluronic Acid
				5.2.2	 Chondroitin Sulfate
				5.2.3	 Folic Acid
		6	 Therapeutic Role of Polymeric Nanoparticles in Macrophage Targeting
			6.1	 Macrophage Targeting in Autoimmune and Autoinflammatory Diseases
			6.2	 Macrophage Targeting in Cancer
			6.3	 Macrophage Targeting to Achieve Metabolic Homeostasis
			6.4	 Macrophage Targeting in Miscellaneous Diseases
		References
	Polymeric Nanoparticles-Based Drug and Gene Delivery to Macrophages
		1	 Introduction
		2	 Challenges of Drug and Gene Delivery to Macrophages Using Polymeric Nanoparticles
			2.1	 Drug/Gene Loading and Release
			2.2	 Endosomal Uptake of Polymeric Nanoparticles and Macrophage Targeting
			2.3	 Targeting of Polymeric Nanoparticles into Phenotype-Specific Macrophages
			2.4	 Protein Corona and Cellular Uptake of Polymeric Nanoparticles
			2.5	 Accumulation of Polymeric Nanoparticles in the Body
		3	 Polymeric Nanoparticles for Drug and Gene Delivery to Macrophages
			3.1	 Polymeric Nanoparticles Designed to Deplete Macrophages
			3.2	 Polymeric Nanoparticles Designed to Modulate the Secretion of Macrophage-Derived Inflammatory Mediators
			3.3	 Polymeric Nanoparticles Designed to Repolarize/Reprogram Macrophages
			3.4	 Polymeric Nanoparticles Designed to Utilize Macrophage as Trojan Horses
		4	 Concluding Remarks and Future Perspectives
		References
	Surface Modification of Nanoparticles for Macrophage Targeting
		1	 Introduction
		2	 Strategies for Macrophage Targeting
		3	 Drug Delivery to the Macrophages Via Targeting Approach
		4	 Macrophage Targeting Via Surface-Engineered Nanocarriers
			4.1	 Microparticles/Microspheres-Mediated Macrophage Targeting
			4.2	 Macrophage Targeting Via Liposomes
			4.3	 Nanoparticles-Mediated Macrophage Targeting
			4.4	 Macrophage Targeting Via Dendrimers
			4.5	 Macrophage Targeting Via Carbon Nanotubes (CNTs)
			4.6	 Macrophage Targeting Via Niosomes
			4.7	 Macrophage Targeting Via Polymerosomes
			4.8	 Surface Modification Strategies for Anticancer Purposes
				4.8.1	 CD163
				4.8.2	 CD204
				4.8.3	 CD206
				4.8.4	 VEGF
				4.8.5	 cMAF
			4.9	 TAM Targeting Ligands for Nanoparticle Surface Modification
				4.9.1	 Small Molecules
				4.9.2	 Oligomers/Saccharide
				4.9.3	 Macromolecules
		5	 Surface Modification Strategies for Lung Infections Via Surface-Modified Nanoparticles Targeting Macrophages
		6	 Surface Modification Strategies for Inflammation
		7	 Surface Modification of Nanoformulations for the Effective Delivery of Drugs to the Macrophage Site
		8	 Macrophage Targeting in Infectious Diseases/Leishmaniasis Therapy
		9	 Macrophage Targeting in Atherosclerosis and Rheumatoid Arthritis
		10	 Future Prospects
		11	 Conclusion
		References
Part III: Lipid Nanoparticles for Macrophage Targeting
	Liposomal Delivery for Targeting Macrophages
		1	 Introduction
		2	 Physicochemical Properties of Liposomes Affecting Drug Delivery and Macrophage Targeting
			2.1	 Phospholipids in Liposome Composition
			2.2	 Size of Liposomes
			2.3	 Surface Charge of Liposomes
			2.4	 Conventional and Modified Liposomes
				2.4.1	 Conventional Liposomes
				2.4.2	 Stealth Liposomes
				2.4.3	 Targeted Liposomes
		3	 Liposome Targeting Macrophages for the Treatment of Various Diseases
			3.1	 Diseases Causing Infection
			3.2	 Cancer and Inflammation Causing Diseases
			3.3	 Cardiovascular Diseases
			3.4	 Cerebral Ischemia and Stroke
		4	 Conclusions
		References
	Solid Lipid Nanoparticles-Based Drug and Gene Delivery to Macrophages
		1	 Introduction
		2	 Nanotechnology in Gene Therapy
		3	 Drug Delivery Systems for Targeted Therapy
		4	 Gene Therapy
		5	 Macrophages
		6	 Macrophages as Therapeutic Targets
		7	 Targeting of Macrophage Receptors
		8	 Solid Lipid Nanoparticles
			8.1	 Preparation of Solid Lipid Nanoparticles
				8.1.1	 Solvent Emulsification/Evaporation Method
				8.1.2	 Double Emulsion Method
				8.1.3	 Homogenization Method
				8.1.4	 Hot Emulsion and Ultrasonication
				8.1.5	 Microemulsion-Based SLN Preparation
				8.1.6	 Supercritical Fluid Technique
			8.2	 SLNs as a Carrier for Gene
			8.3	 SLNs as a Drug Carrier
			8.4	 Surface Modifications of SLNs to Target Macrophages
			8.5	 Enhancement of Transfection Efficiency
			8.6	 Characterization of Transfection Agents
				8.6.1	 Physicochemical Properties: Particle Size, Zeta Potential, and Morphology
				8.6.2	 Adsorption Efficiency
				8.6.3	 Circular Dichroism Studies
				8.6.4	 Exposure of Transfection Agents to Nucleases
				8.6.5	 In Vitro Release Studies
				8.6.6	 Cytotoxicity Assays
				8.6.7	 Cellular Uptake Assays and Internalization Pathways
				8.6.8	 In Vitro Transfection Assay
				8.6.9	 Hemagglutination Assay
		9	 Conclusion
		References
	In Vivo Fate of Nanoparticles Undergoing Macrophage Targeting
		1	 Introduction
		2	 What Is a Macrophage?
			2.1	 Origin of Macrophages
			2.2	 Polarization of Macrophages
				2.2.1	 Polarization of M1 Macrophages into Acquired and Innate Forms
				2.2.2	 Polarization of M2 Macrophages
				2.2.3	 Regulation of Macrophage Polarization
		3	 Methods to Study Uptake of Various Delivery Systems by Macrophages
			3.1	 Electron Microscopy
			3.2	 Super-Resolution Microscopy
			3.3	 Single-Particle Tracking
			3.4	 Intravital Microscopy
			3.5	 Two-Photon Microscopy
			3.6	 In Situ Hybridization
			3.7	 Nuclear Imaging
		4	 How Do Macrophages Identify Nanoparticles?
			4.1	 Toll-Like Receptors (TLR)
			4.2	 Mannose/Lectin Receptors
			4.3	 Scavenger Receptors
			4.4	 Fc Receptors
		5	 Opsonization of Nanoparticles
			5.1	 Factors Affecting Opsonization
				5.1.1	 Surface Property of NP
				5.1.2	 Surface Curvature
				5.1.3	 Surface Topography
				5.1.4	 Size
		6	 Endocytosis of Nanoparticle
			6.1	 Pinocytosis
				6.1.1	 Clathrin-Dependent Endocytosis
				6.1.2	 Caveolin-Dependent Endocytosis
				6.1.3	 Macropinocytosis
			6.2	 Phagocytosis
		7	 Processing of Nanoparticles
		8	 Interaction of Nanoparticles
			8.1	 Interaction with Phospholipids
				8.1.1	 Inside the Lungs
				8.1.2	 With Bilayer Membranes
			8.2	 Interaction with the Proteins
			8.3	 Interaction with the DNA
			8.4	 Interaction with Small Biomolecules
		9	 Functional Changes Induced by Nanoparticles
			9.1	 Changes in Plasma Membrane
			9.2	 Changes in Ion Channel
			9.3	 Changes in Cytoskeleton
			9.4	 Changes in Mitochondria
			9.5	 Changes in the Nucleus
		10	 Exocytosis of Nanoparticles
			10.1	 Factors Affecting Exocytosis of Nanoparticles
		11	 Macrophage Targeting by Nanoparticles in Various Diseases
			11.1	 For Human Immunodeficiency Virus
			11.2	 For Diseases Related to Inflammation
			11.3	 For Diseases Related to Neuroinflammation
			11.4	 For Diseases Related to Bacterial Infection
		12	 Effect of Physicochemical Properties on In Vivo Fate of Nanomaterials
			12.1	 Effect of Size
			12.2	 Effect of Shape
			12.3	 Charge on Nanoparticles
			12.4	 Elasticity of Nanoparticles
			12.5	 Surface Hydrophobicity
		13	 Adverse Reactions
			13.1	 Complement Activation
			13.2	 Thrombotic Activation
			13.3	 Systemic Inflammatory Effects
		14	 Toxicity of Nanomaterials
		15	 Conclusion and Future Perspectives
		References
	Nanoparticles-Based Theranostics for Macrophage Targeting
		1	 Introduction
		2	 Imaging Modalities for Nanotheranostics
			2.1	 Optical Imaging
			2.2	 Magnetic Resonance Imaging (MRI)
				2.2.1	 H MRI
				2.2.2	 F MRI
			2.3	 Nuclear Imaging
			2.4	 Multimodal Imaging
			2.5	 Radionuclide Imaging Technique
			2.6	 Computed Tomography
			2.7	 Ultrasound
		3	 Different Types of Nanoparticles Used in Imaging
			3.1	 Drug Conjugates and Complexes
			3.2	 Dendrimers
			3.3	 Vesicles
			3.4	 Micelle
			3.5	 Core Shell
			3.6	 Microbubbles
			3.7	 Carbon Nanotubes
		4	 Various Types of Theranostic Agents
			4.1	 Iron Oxide Nanoparticle–Based Theranostic Agents
			4.2	 Quantum Dots–Based Theranostics Agents
			4.3	 Gold Nanoparticles–Based Theranostic Agent
			4.4	 Carbon Nanotube-Based Theranostic Agents
			4.5	 Silica Nanoparticles–Based Nanotheranostic Agents
		5	 Targeting Theranostics Agent Against Various Diseases
			5.1	 Targeting Theranostics Agent Against Cancer
				5.1.1	 Targeting Theranostics Agent Against Breast Cancer
				5.1.2	 Targeting Theranostics Agent Against Ovarian Cancer
			5.2	 Targeting Theranostics Agent Against Rheumatoid Arthritis
			5.3	 Targeting Theranostics Agent Against Atherosclerosis
			5.4	 Targeting Theranostics Agent Against AIDS
			5.5	 Targeting Theranostics Agent Against Diabetes
			5.6	 Targeting Theranostics Agent Against IBD and Other Inflammatory Disease
		6	 Challenges in Nanotheranostics
		7	 Conclusion
		References
Part IV: Targeting Macrophages for Treatment of Various Diseases
	Tumor-Associated Macrophages: Therapeutic Targets of Cancer
		1	 Introduction
		2	 Macrophages and Tumor-Associated Macrophages (TAMs)
		3	 TAMs and Cancers
			3.1	 Crosstalk of TAMs and Cancer Cells in TME
			3.2	 TAMs and Tumor Progression
			3.3	 TAMs and Tumor Metastasis
			3.4	 TAMs and Angiogenesis
		4	 TAMs in Cancer Therapy
			4.1	 TAMs in Radiotherapy
			4.2	 TAMs in Chemotherapy
			4.3	 TAMs in Cancer Immunotherapy
			4.4	 TAMs Aid Precision Cancer Treatment
		5	 Target TAMs for Cancer Therapy
			5.1	 Target TAMs Recruitment and Localization for Cancer Therapy
				5.1.1	 Targeting CSF-1/CSF-1R Signaling
				5.1.2	 Targeting CCL-2/CCR-2 Axis
				5.1.3	 Targeting CXCL-12/CXCR-4 Axis
				5.1.4	 Targeting VEGF/VEGFR Signaling
			5.2	 Target TAMs Inhibition for Cancer Therapy
			5.3	 Reprogramming TAMs for Cancer Therapy
				5.3.1	 TLR Agonists to Reprogram TAMs
				5.3.2	 Reprogramming TAMs by mAb and Fusion Protein
				5.3.3	 Other Strategies to Reprogram TAMs
			5.4	 TAM as Drug Delivery Systems
				5.4.1	 M1 Macrophages as Drug Carriers
				5.4.2	 M1 Macrophages-Derived Exosomes as Drug Carriers
				5.4.3	 Nanoparticles Coated with M1 Macrophage Membrane as Drug Carriers
		6	 Conclusions
		References
	Macrophage Targeting by Nanocarriers for Therapy of Autoimmune Diseases
		1	 Introduction
		2	 Understanding the Macrophage Lineage
			2.1	 Role of Macrophages in Autoimmune Diseases
				2.1.1	 Rheumatoid Arthritis (RA)
				2.1.2	 Systemic Lupus Erythematosus (SLE)
				2.1.3	 Sjögren’s Syndrome (SS)
				2.1.4	 Multiple Sclerosis (MS)
		3	 Role of Macrophage Receptor in Autoimmune Diseases
		4	 Nanoparticles-Mediated Macrophage Targeting
			4.1	 Liposomes-Mediated Macrophage Targeting
			4.2	 Polymeric Nanoparticles-Mediated Macrophage Targeting
			4.3	 Dendrimers-Mediated Macrophage Targeting
			4.4	 Metallic Nanoparticles-Mediated Macrophage Targeting
			4.5	 Lipid Nanoparticles–Mediated Macrophage Targeting
		5	 Conclusion
		References
	Macrophage Targeting for Therapy of Cardiovascular Diseases (CVD)
		1	 Origins and Functions of Cardiac Tissue-Resident Macrophages in the Normal Heart Under Healthy and Physiological Condition
			1.1	 Origin of Cardiac-Resident Macrophages in the Normal Heart (Healthy and Physiological Condition)
			1.2	 Functions of Cardiac-Resident Macrophages in Physiological Condition
				1.2.1	 Involvement of Coronary Artery Development and Maturation
				1.2.2	 Obligatory Role in Valvular Development and Remodeling
				1.2.3	 Facilitation of Electrical Conduction in the Heart
				1.2.4	 Promotion of Cardiac Regeneration
		2	 Origins and Functions of Cardiac Tissue-Resident Macrophages in the Heart Subjected to Pathophysiological Condition
			2.1	 Origin of Cardiac-Resident Macrophages in Pathophysiological Condition
			2.2	 Functions of Macrophages in Pathophysiological Condition
				2.2.1	 Recruitment of Monocytes to the Heart
				2.2.2	 Cardiac Diastolic Dysfunction in Hypertension-Induced Chronic Heart Failure
				2.2.3	 Nonischemic Cardiomyopathy
				2.2.4	 Myocardial Infarction (MI)
				2.2.5	 Microglia/Macrophages and Ischemic Brain Injury (Focal Cerebral Ischemia) − Stroke
				2.2.6	 Hemorrhagic Stroke − Spontaneous Intracerebral Hemorrhage
				2.2.7	 Macrophages and Atherosclerosis
		3	 Pharmacological Interventions for Targeting Macrophages for CVD
			3.1	 CCR2 Antagonists
				3.1.1	 RS-504393
				3.1.2	 INCB3344
			3.2	 MCP-1/CCL2 Competitive Inhibitor – PA508
			3.3	 M2 Macrophage Plasticity Modulator – Azithromycin
		References
	Delivery of Oligonucleotide Therapeutics for Macrophage Reprogramming in Inflammatory Diseases
		1	 Macrophage Biology and Phenotypes in Health and Disease
		2	 Targeting Tissue-Resident Versus Infiltrating Macrophages
			2.1	 Tissue-Resident Macrophages (TRMs) and Infiltrating Macrophages (IMs) in Disease Progression and Therapy
				2.1.1	 IMs in Propagating Acute Liver Injury
				2.1.2	 Illustrative Example of TRM/Kupfer Cell-Targeted Therapy for NAFLD
		3	 Oligonucleotide Therapeutics
			3.1	 Classification of Oligonucleotide-Based Therapies
				3.1.1	 RNase-H-Dependent Antisense Oligonucleotides (ASOs)
				3.1.2	 Exon Skipping Antisense Oligonucleotides
				3.1.3	 Small Interfering RNAs (siRNAs)
				3.1.4	 MicroRNA Mimics and Anti-MicroRNAs
			3.2	 Challenges to Oligonucleotide-Based Delivery Approach
		4	 Macrophage-Specific Delivery Strategies
			4.1	 Nanoparticle-Based Macrophage Delivery
			4.2	 Receptor-Mediated Oligonucleotide Delivery Using Ligand Conjugates
		5	 Inference
		References
	Macrophage-Targeted Chemotherapy for Tuberculosis
		1	 Tuberculosis (TB): An Insight
		2	 Macrophage: The Cellular Tropics of Mycobacterium tuberculosis
			2.1	 Receptor-Mediated Endocytosis
			2.2	 Receptor-Mediated Phagocytosis
		3	 Challenges with Current Chemotherapy and Emergence of MDR-TB and XDR-TB
		4	 Need for Drug Designing, Engineered Nanoconstructs, and Macrophage-Targeted Chemotherapy
			4.1	 Passive Drug Targeting
			4.2	 Active Drug Targeting
				4.2.1	 Mannose Receptor-Mediated Macrophage Targeting
				4.2.2	 Hyaluronic Acid Receptor-Mediated Macrophage Targeting
				4.2.3	 Folate Receptor-Mediated Macrophage Targeting
				4.2.4	 Tuftsin Receptor-Mediated Macrophage Targeting
				4.2.5	 Formyl Peptide Receptors-Mediated Macrophage Targeting
				4.2.6	 Other Receptors-Mediated Macrophage Targeting
		5	 Concluding Remarks and Future Prognosis
		References
	Macrophage-Targeted Chemotherapy for Respiratory Diseases Other Than Tuberculosis
		1	 Introduction
			1.1	 Respiratory System
		2	 Population of Respiratory Macrophage
			2.1	 Alveolar Macrophages (AMs)
			2.2	 Interstitial Macrophages (IMs)
			2.3	 Dendritic Cells
			2.4	 Monocytes
		3	 Respiratory Tract and Infection
			3.1	 Microbiota
		4	 Respiratory Disorders/Diseases
			4.1	 Understanding Respiratory Disorders
			4.2	 Asthma
			4.3	 COPD
			4.4	 Pulmonary Fibrosis
			4.5	 Lung Cancer
		5	 Way to Reach Macrophages
		6	 Macrophage as Therapeutic Target
			6.1	 Nanocarriers for Macrophage Targeting
				6.1.1	 Criteria for Macrophage Targeting
				6.1.2	 Lipid-Based Nanoparticles
					Liposomes
					Solid Lipid Nanoparticles (SLN)
					Polymeric Nanoparticles for AMs Targeting
					Macrophage Targeting in Lung Cancer
		7	 Final Remark
		References
	Macrophage Targeting for Therapy of Intraocular Diseases
		1	 Introduction
			1.1	 Anatomical and Physiological Features of the Eye
			1.2	 The Lachrymal System
			1.3	 Barriers Restricting Intraocular Drug Transport
				1.3.1	 Tear
				1.3.2	 Cornea
				1.3.3	 Conjunctiva
				1.3.4	 Sclera
				1.3.5	 Choroid/Bruch’s Membrane
				1.3.6	 Retina
				1.3.7	 Blood-Retinal Barrier
		2	 Ocular Drug Delivery
		3	 Immunoregulatory Role of Ocular Macrophages
		4	 Macrophages at Diseased Intraocular Sites
			4.1	 Corneal Macrophages
				4.1.1	 Distribution and Phenotype
				4.1.2	 Role in Homeostasis
				4.1.3	 Role in Pathology
			4.2	 Macrophages in the Uveal Tract
				4.2.1	 Iris and Ciliary Body Macrophages
				4.2.2	 Role in Homeostasis and Pathology
			4.3	 Choroidal Macrophages
				4.3.1	 Distribution and Phenotype
				4.3.2	 Role in Pathology
			4.4	 Retinal Microglia
				4.4.1	 Distribution and Phenotype
				4.4.2	 Targeting Microglia for the Treatment of Retinal Degenerative Diseases
				4.4.3	 Functions of Retinal Microglia
				4.4.4	 Phagocytosis
			4.5	 Other Ocular Macrophages
		5	 Nanocarriers for Macrophage Targeting in Ocular Diseases
			5.1	 Polymeric Nanoparticles
			5.2	 Polymeric Micelles
			5.3	 Dendrimers
			5.4	 Liposomes
			5.5	 Nanostructured Lipid Carriers
			5.6	 Niosome
		6	 Conclusion
		References
	Macrophage Targeting for Therapy of HIV
		1	 Introduction
			1.1	 Entry of HIV-1 into Macrophages
			1.2	 Reverse Transcription and Various Factors Restricting in Host
			1.3	 Nuclear Transport
			1.4	 Transcription of HIV-1
			1.5	 Assembly of HIV-1 in Macrophages
		2	 HIV Protein Interaction with Cell Signalling in Macrophages
			2.1	 Tat (Trans-Activator of Transcription)
			2.2	 Viral Protein R (Vpr)
			2.3	 Nef
		3	 Macrophage Contribution in HIV-1 Pathogenesis
			3.1	 CTLs (Cytotoxic T cells) and Macrophages
		4	 Agents Inducing Apoptosis in HIV-Infected Macrophages
		5	 Conventional HIV-1 Therapies in Macrophages
			5.1	 RTIs (Reverse Transcriptase Inhibitors)
			5.2	 Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
			5.3	 Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
			5.4	 Inhibitors for Integrase
			5.5	 Inhibitors for Protease Inhibitors (PIs)
			5.6	 Entry/Fusion Inhibitors
		6	 Novel Therapies Against HIV-1 in Macrophages
			6.1	 Carbohydrate-Binding Agents (CBAs)
			6.2	 PI3K/Akt Interference Agents
			6.3	 Small Interfering RNA (siRNA)
			6.4	 Immune-Based Treatment
			6.5	 IL-27, an Anti-HIV Cytokine
			6.6	 Nanocarriers Targeting HIV
				6.6.1	 Liposomes
				6.6.2	 Nanoparticles
				6.6.3	 Dendrimers
				6.6.4	 Bioconjugates
				6.6.5	 Solid Lipid Nanoparticles (SLNs)
				6.6.6	 Ethosomes
		7	 HIV-1 and Cells of CNS, i.e., Myeloid
		8	 Flushing Out Therapy
		9	 Conclusion
		References
Part V: Specific Therapeutics and Clinical Trials on Macrophage Targeted Delivery
	Delivery of siRNA to Macrophages: Challenges and Opportunities
		1	 Introduction
		2	 Background
			2.1	 Macrophages
			2.2	 Small Interfering Ribonucleic Acid (siRNA)
			2.3	 siRNA-Targeted Therapies
		3	 Targeted Delivery System—siRNA
			3.1	 Importance of Targeted Delivery Systems
			3.2	 The Barriers of siRNA
		4	 Therapeutic Applications
			4.1	 Current Therapeutic Applications
			4.2	 The Use of Targeted Delivery Systems to Macrophages
		5	 Current siRNA Targeted Deliveries for Therapeutic Systems
			5.1	 siRNA Delivery for Ocular Use
		6	 Conclusion
		References
	Role of Macrophages and Immunotherapy in Wound Healing
		1	 Introduction
		2	 Function of the Skin
		3	 Wound Macrophages
		4	 Role of Macrophages in Inflammation and Tissue Formation
		5	 Role of Macrophages in Tissue Reorganization
		6	 Chronic Wounds and Tumors
		7	 Factors Affecting Wound Healing
		8	 Conclusion
		9	 Future Trends
		References
	Effects of Mycotoxins on Macrophages and Their Possible Clinical Implications
		1	 Introduction
		2	 Ergot Toxin
		3	 Aflatoxin
		4	 Trichothecene Toxin
		5	 Mycophenolic Acid Toxin
		6	 Ochratoxin
		7	 Summary
		References
	Recent Trends in Clinical Studies on Macrophage-Targeted Delivery
		1	 Introduction: The Central Role of Macrophages in Human Biology
		2	 Select Aspects of Macrophage Biology
			2.1	 The Role of the Macrophage in the Phagocytic Response
			2.2	 Diversity and Adaptation of the Macrophage Response
			2.3	 Clinical Implications of Macrophage Diversity
		3	 Clinical Trials of Drug Delivery Systems Targeting Macrophages in Tumors and Cancer
			3.1	 Clinical Trials Targeting Macrophages in Cancer
				3.1.1	 The CD47-SIRPα Pathway
				3.1.2	 The CD40 Pathway
				3.1.3	 Drug Delivery Strategies
		4	 The Role of Macrophages in Driving Cardiovascular Diseases: Myocardial Infarction, Myocarditis, Arrhythmia, and Atherosclerosis
			4.1	 Clinical Trials for Canakinumab: Targeting the Cardiovascular Inflammatory Milieu
		5	 Conclusion
		References
Index