Polymeric Micelles: Principles, Perspectives and Practices

Preface
Contents
Editors and Contributors
1: Synthesis, Self-Assembly, and Functional Chemistry of Amphiphilic Block Copolymers
	1.1 Introduction
	1.2 Different Molecular Parameters of Amphiphilic Block Copolymers Affecting Micellar Traits
		1.2.1 Self-Assembling of Amphiphilic Block Copolymers
	1.3 Structural Modifications
	1.4 Synthesis of Copolymers
	1.5 Synthetic Advancements in Synthesis of ABCs
		1.5.1 Modification of Amphiphilic Block Copolymers for Drug Targeting Using Functional Moieties
	1.6 Conclusion
	References
2: Advances in Polymer Optimization for Enhanced Drug Delivery
	2.1 Introduction
	2.2 Types of Polymers Used
		2.2.1 Diblock Copolymer
		2.2.2 Graft Copolymers
		2.2.3 Triblock Copolymer
			2.2.3.1 Symmetric Triblock Copolymers for Micelle Preparation
			2.2.3.2 Asymmetric Triblock Copolymers for Micelle Preparation
	2.3 Role of Various Polymers in Achieving Target-Specific Drug Release
		2.3.1 Polymers Used for the Micelles Sensitive to Internal Triggers
			2.3.1.1 Polymers Used to Prepare Mucoadhesive Micelles
				Chitosan
				Gelatin
				Hyaluronic Acid (HA)
			2.3.1.2 Polymers Used to Prepare Enzymatically Triggerred Polymeric Micelles
			2.3.1.3 Polymers Used to Prepare Redox Triggered Polymeric Micelles
			2.3.1.4 Polymers Used to Prepare pH-Sensitive Polymeric Micelles
				Poly(Styrene-Alt-Maleic Anhydride) Furfurylamine (PHSM/f)
				Poly(Ethylene Glycol)-Poly(Aspartate-Hydrazone Adriamycin) [PEG-p(Asp-Hyd-Adr)]
				Polyacrylic Acid (PAAc)
				Poly(N,N′-Dimethyl Aminoethyl Methacrylate) (PDMAEMA)
				Poly(4-Vinylpyridine) (PVP)
				Poly(Histidine) PHIS
				Poly(β-Amino Ester) (PβAE/PAE)
			2.3.1.5 Polymers Used to Prepare Heat-Sensitive Polymeric Micelles
		2.3.2 Polymeric Micelles Sensitive to External Stimulus
			2.3.2.1 Photosensitive Polymeric Micelles
			2.3.2.2 Magnetic-Sensitive Polymeric Micelles
	2.4 Conclusions and Future Directions
	References
3: Dynamics of Micelle Formation
	3.1 Introduction
	3.2 Factors Influencing Micelle Formation Dynamics
		3.2.1 Amphiphilic Block Copolymer
		3.2.2 Micelle Size and CMC
		3.2.3 Hydrogen Bonding
	3.3 Theories of Micelle Formation
		3.3.1 Law of Mass Action
		3.3.2 Flory-Huggin´s Interaction Parameters
		3.3.3 Molecular Dynamics
		3.3.4 Quantitative Structure-Property Relationship
	3.4 Thermodynamics of Micelle Formation
	3.5 Techniques to Evaluate Micelle Formation Dynamics
		3.5.1 Isothermal Titration Calorimetry
		3.5.2 Förster Resonance Energy Transfer
		3.5.3 Conductometry
		3.5.4 Dissipative Particle Dynamics
	3.6 Conclusion
	References
4: Types of Polymeric Micelles for Controlled Drug Release
	4.1 Introduction
	4.2 Types of Polymeric Micelles
		4.2.1 Hypoxia-Responsive Polymeric Micelles
		4.2.2 Glucose-Sensitive Polymeric Micelles
		4.2.3 Reduction-Sensitive Polymeric Micelles
		4.2.4 pH-Sensitive Polymeric Micelles
		4.2.5 Enzyme-Responsive Polymeric Micelles
		4.2.6 Dual-Responsive Polymeric Micelles
		4.2.7 Multi-Responsive Polymeric Micelles
		4.2.8 Polymeric Micelles Used in Imaging and Detection
	4.3 Types of Polymeric Micelles Depending on Their Application
		4.3.1 Nucleic Acid-Based Polymeric Micelles
		4.3.2 Phytoconstituent-Loaded Polymeric Micelles
		4.3.3 Surface-Engineered Polymeric Micelles
		4.3.4 Ligand-Conjugated Polymeric Micelles
		4.3.5 Protein-Based Polymeric Micelles
		4.3.6 Biosensor-Based Polymeric Micelles
	4.4 Conclusion
	References
5: Drug Solubilization and Drug Release from Polymeric Micelles
	5.1 Introduction
	5.2 Drug Release from Micelles
	5.3 Role of Micelles in Protecting Drugs from the Biological Environment
	5.4 Factors Affecting the Solubilization of Drugs in Micelles
		5.4.1 Use of Concentration of Surfactant above the CMC Level
		5.4.2 Addition of Salt or Electrolyte
		5.4.3 Temperature
		5.4.4 Effect of pH
		5.4.5 Position of Solubilizate in Micellar Structure
		5.4.6 Use of Mixed Micelles
		5.4.7 Structure of Surfactant
	5.5 Advantages over Conventional Drug Delivery
	5.6 Role of Functionalized Micelles in Various Diseases
		5.6.1 Cancer
		5.6.2 Neurological Disorders
		5.6.3 Infectious Diseases
		5.6.4 Pulmonary Diseases
		5.6.5 Imaging and Diagnosis
	5.7 Summary
	References
6: Physical and Analytical Techniques Used for the Characterization of Polymeric Micelles
	6.1 Introduction
	6.2 Physical and Analytical Characterization of Polymeric Micelles
		6.2.1 Microscopic Techniques
			6.2.1.1 Atomic Force Microscopy
			6.2.1.2 Scanning Electron Microscopy
			6.2.1.3 Transmission Electron Microscopy
			6.2.1.4 Confocal Laser Scanning Microscopy
		6.2.2 Spectroscopic Techniques
			6.2.2.1 Fourier-Transform Infrared Spectroscopy
			6.2.2.2 Nuclear Magnetic Resonance
		6.2.3 Scattering Techniques
			6.2.3.1 Dynamic Light Scattering
			6.2.3.2 Small Angle Neutron Scattering (SANS)
		6.2.4 Other Potential Techniques
			6.2.4.1 Differential Scanning Calorimetry
			6.2.4.2 X-Ray Diffraction
			6.2.4.3 Critical Micellar Concentration
	6.3 Conclusion
	References
7: Stimuli-Sensitive Polymeric Micelles for Biomedical Applications
	7.1 Introduction
	7.2 pH-Responsive Polymeric Micelles for Drug Delivery and Theranostics
	7.3 Glucose-Responsive Polymeric Micelles for Drug Delivery
	7.4 ROS: Responsive Polymeric Micelles for Theranostics
	7.5 Redox Responsive Polymeric Micelles for Drug Delivery and Theranostics
	7.6 Hypoxia Responsive Polymeric Micelles for Drug Delivery and Theranostics
	7.7 Enzyme-Responsive Polymeric Micelles for Drug Delivery and Theranostics
	7.8 Dual-Responsive Polymeric Micelles for Drug Delivery and Theranostics
	7.9 Multi-Responsive Polymeric Micelles for Drug Delivery and Theranostics
	7.10 Extrinsic Stimuli-Responsive Polymeric Micelles for Drug Delivery and Theranostics
	7.11 Conclusion
	7.12 Future Prospects
	References
8: Nucleic Acid-Based Micellar Therapy for the Treatment of Different Diseases
	8.1 Background
	8.2 Nucleic Acid Based Micellar Therapy
	8.3 Treatment Strategies for Nucleic-Acid-Based Micellar Therapy
	8.4 Diseases Associated with the Genetic Mutation
		8.4.1 Cancer
			8.4.1.1 Characteristics Strategies for Gene Therapy for Cancer
		8.4.2 DM
		8.4.3 AIDS
		8.4.4 Hereditary Diseases
	8.5 Conclusion & Future Aspects
	References
9: Polymeric Micelles in the Delivery of Therapeutic Phytoconstituents
	9.1 Introduction
	9.2 Micelles
	9.3 Polymeric Micelles
	9.4 Polymers Used in the Preparation of Polymeric Micelles
	9.5 Mechanism of Micelle Formation
	9.6 Phytoconstituents
	9.7 Role of Nanocarriers for Delivery of Phytoconstituent
	9.8 Application of Polymeric Micelles for Delivery of Phytoconstituent
		9.8.1 Anticancer Agent
		9.8.2 Antibacterial Agent
		9.8.3 Antidiabetic Treatment
		9.8.4 Antifungal Treatment
		9.8.5 Antimalarial Treatment
	9.9 Future Prospective
	9.10 Conclusion
	References
10: Diagnostic Applications of Surface-Engineered Polymeric Micelles
	10.1 Introduction
	10.2 Diagnostic Applications
		10.2.1 Diagnosis of Tumour
		10.2.2 Diagnosis of Glucose
		10.2.3 Diagnosis of Neuronal Diseases
	10.3 Conclusion
	References
11: Ligand Conjugated Polymeric Micelles for Targeted Delivery of Drug Payloads in Cancer Therapy
	11.1 Introduction
	11.2 Active Targeting of Tumors
	11.3 Various Ligands for Active Targeting
		11.3.1 Antibodies Targeted Polymeric Micelles
		11.3.2 Folate-Conjugated Polymeric Micelles
		11.3.3 Chitosan Conjugated Polymeric Micelles
		11.3.4 RGD Peptide Conjugated Polymeric Micelles
		11.3.5 Transferrin and Epidermal Growth Factor Conjugated Polymeric Micelles
	11.4 Conclusion
	References
12: Polymeric Micelles in the Delivery of Proteins
	12.1 Introduction
	12.2 Polymeric Micelles (PM) as Therapeutic Carriers for Protein Delivery
	12.3 Advantages and Challenges of Polymeric Micelles (PM) for the Delivery of Proteins
	12.4 Oral Uptake of Polymeric Micelles (PM)
	12.5 Types of Polymers Utilized in the Administration of Micellar Drugs
	12.6 Stimuli Sensitive Micelles for Delivery of Protein
	12.7 Polymeric Micelles (PM) for Multiple Functionality and Protein Delivery
	12.8 Co-delivery of Drugs and siRNA Using Multifunctional Micelles
	12.9 Conclusion
	References
13: Regulatory Aspects for Polymeric Micelles
	13.1 Introduction
	13.2 The Importance of Regulation
		13.2.1 Properties and Recent Updates of PMs
	13.3 Perspective from a Regulatory Standpoint on the Creation of Nanomedicines or Polymeric Micelles
	13.4 A Versatile Drug Delivery Carrier: Polymeric Micelles
		13.4.1 Regulatory Aspects
		13.4.2 Regulatory Guidelines, eCTD Submission in Various Countries
	13.5 Nanotechnology Regulatory Challenges
	13.6 Regulation of Nanotechnology-Based Pharmaceuticals
		13.6.1 Specified Polymeric Micelles for PMs and Injectables
	13.7 Conclusion
	References
14: Toxicological and Regulatory Challenges in Design and Development of Polymeric Micelles
	14.1 Introduction to Nanotechnology in Drug Delivery
	14.2 Polymeric Nanoparticles as Drug Delivery System
	14.3 Clinically Approved Polymeric Nano Formulation
	14.4 Development of Polymeric Micelles
		14.4.1 Design Considerations
		14.4.2 Toxicity Issues
		14.4.3 Ethical Issues in Clinical Trials
		14.4.4 Regulatory Aspects
	14.5 Conclusion
	References
15: Stability of Polymeric Micelles and Their Regulatory Status
	15.1 Introduction
	15.2 Safety of PMs
		15.2.1 PMs Composition
		15.2.2 PMs Structure
		15.2.3 Interaction of PMs with the Biological Systems
		15.2.4 Administration Routes of PMs
		15.2.5 Regulatory Aspects of PMs
	15.3 Physicochemical and Kinetic-Related Stability Aspects of PMs
		15.3.1 Physicochemical Stability
			15.3.1.1 Thermodynamic Stability
			15.3.1.2 Impact of a Hydrophobic Segment on Micelles Stability
			15.3.1.3 Impact of Encapsulated and Conjugated Drug
			15.3.1.4 Environmental Impact on the Stability
		15.3.2 Kinetic Stability
	15.4 Conclusion
	References