This book thoroughly reviews the advancements in design and applications of Polymeric Micelles (PMs) in drug delivery. It provides information on the synthesis of amphiphilic block copolymers and their types, functional chemistry for targeting and sensing, and biomedical applications. The book further provides the possibilities for designing PMs in a range of drug delivery approaches. The book addresses the molecular parameters of amphiphilic block copolymers that are required for functionalizing PMs for drug delivery applications. Additionally, the book presents recent advances in applications of PMs such as co-delivery, sensing, theranostics, delivery of nucleic acids, and proteins. Towards the end, it discusses different physico-chemical strategies to enhance the stability and drug retention of polymeric micelles and reviews the preclinical and clinical toxicity and immunogenicity-related aspects of polymeric micelles. This book is an invaluable source for academics, research, and industry professionals working in the field of polymeric micelles and drug delivery.
Author(s): Sachin Kumar Singh, Monica Gulati, Srinivas Mutalik, Muralikrishnan Dhanasekaran, Kamal Dua
Publisher: Springer
Year: 2023
Language: English
Pages: 300
City: Singapore
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
