Liposomes in Drug Delivery

Liposomes in Drug Delivery: What, Where, How and When to Deliver is a concise, well-structured reference covering all the important issues related to the potential of this technology. Organized to provide practical information to researchers from any discipline with a particular therapeutic or bio-active substance to deliver, this book helps readers understand if liposomes can be of benefit for their particular need, what is the best type of liposome to use according to what needs to be delivered, where/when to deliver it, and how to design/prepare/characterize/investigate/optimize liposome properties for a particular application.

The book is structured in Four parts. The first covers in a concise but in-depth way, what liposomes are, which are the liposome types, advantages/disadvantages, and what is their stability, characterization methods, in vitro stability, and in vivo fate after different administration methods (routes). The second part focuses on the different mechanisms for liposomal drug delivery. Methodologies/technologies for manipulation of liposome structure/properties in order to design liposomes for particular delivery applications. Specific roadmaps for liposome design are discussed, including components to incorporate in liposomes for specific types of encapsulated molecules or specific routes of administration. The third part covers liposome applications for drug delivery. It focuses on specific delivery considerations for particular diseases. Finally, the fourth part covers methods of liposome fabrication.

Cover image
Title page
Table of Contents
Copyright
Dedication
Contributors
Foreword
Preface
Acknowledgments
Chapter 1. Introduction to liposome assisted drug delivery
1.1. Introduction
1.2. What are liposomes? A trip through liposome evolution
1.3. What types of drugs or active substances can liposomes deliver?
1.4. Where can liposomes deliver drugs to?
1.5. How can liposomes deliver the drugs/active substances to the intended sites?
1.6. How are liposomes prepared/loaded with drugs and characterized?
1.7. When is delivery of drugs/active substances via liposomal formulations useful?
1.8. Summary
Chapter 2. Basic concepts of liposomes: Components, structures, properties and classification
2.1. Introduction
2.2. Liposome components, structure, and properties
2.3. Classifications of liposomes
Chapter 3. Liposome characterization methodologies (physical and chemical methods)
3.1. Introduction
3.2. Methods applied for size distribution
3.3. Surface charge/properties
3.4. Drug release, integrity, and stability
3.5. Osmolarity and pH
3.6. Summary
Chapter 4. Morphological assessment of liposomes by microscopy
4.1. Introduction
4.2. Negative staining
4.3. Freeze fracture electron microscopy
4.4. Light microscopy
4.5. Dynamic light scattering
4.6. Small angle X-ray scattering
4.7. Fluorescent spectroscopy
4.8. Atomic force microscopy
4.9. Cryo-electron microscopy
4.10. Liposomal characterizations in drug delivery
4.11. Conclusion
Chapter 5. Liposome stability and integrity
5.1. Introduction
5.2. Insights on the membrane fluidity of liposomes
5.3. Intrinsic/external factors affecting membrane fluidity and liposomes stability
5.4. Methods to assess membrane fluidity
5.5. Membrane integrity and methods to assess it
5.6. Physical stability of liposomes: factors implicated in colloidal stability and novel stabilization strategies
5.7. Chemical stability of liposomes and stabilization approaches
5.8. Liposome-based mRNA vaccines for COVID-19
5.9. Summary
Chapter 6. In vivo fate of liposomes: Biodistribution and cell membrane interactions
6.1. Introduction
6.2. Pharmacokinetics of liposomes
6.3. Absorption of liposomal formulations via various routes of administration
6.4. Distribution of liposomes
6.5. Clearance of liposomes from the systemic circulation
6.6. In vivo behavior of liposomes
6.7. Factors affecting the liposomal pharmacokinetic behavior
6.8. The bottleneck for translation into clinical practice
6.9. Summary and conclusions
Acknowledgments
Chapter 7. Liposomes in controlled drug delivery: Controlling drug release kinetics and biodistribution/pharmacokinetics
7.1. Introduction
7.2. Release of drugs/active substances from liposomes and factors affecting drug release
7.3. Controlling the release of drugs/active substances from liposomes
7.4. Controlling the time and place where the drug will be released: Targeting
7.5. Smart delivery: Stimuli-responsive liposomes
7.6. Successful and unfinished stories
7.7. Promises
Chapter 8. Liposome surface modifications-engineering techniques
8.1. Introduction
8.2. Importance and advantage of polymer coating for liposomes
8.3. Engineering techniques for coupling ligands
8.4. Innate immunity activation
8.5. Alternative method to PEG coating using phospholipid polymer derivatives
8.6. Future perspective
Chapter 9. Activatable liposomes: Ultrasound-activated liposomes and lipid vesicles
9.1. Introduction: Nanoparticles advanced in the clinic for cancer treatment
9.2. Fundamentals of tissue penetrating focused ultrasound
9.3. Focused ultrasound causing thermal activated liposome drug release in tumors
9.4. Activatable liposomes as theranostic agents
9.5. Cavitation activatable gas containing lipid vesicles as theranostics agents
9.6. Conclusions
Chapter 10. Liposomes for drug delivery to the brain
10.1. Introduction
10.2. Methods of transport across BBB
10.3. Direct nose-to-brain route
10.4. Advancements in liposome-based approaches for brain targeting
10.5. Liposomes as diagnostic tools
10.6. Current challenges and future perspectives
Chapter 11. Liposomes for drug delivery to cancer cells
11.1. Introduction
11.2. Agents delivered by liposomes and liposome delivery properties
11.3. Delivery targets and first steps toward dosimetry-informed personalized treatments
11.4. Routes of administration
11.5. Chapter review
Chapter 12. Liposomes as vaccine delivery systems
12.1. Introduction on liposomes used as a vaccine adjuvant-delivery systems
12.2. Liposomes used for delivering mRNA vaccines
12.3. Liposome-delivered subunit vaccines
12.4. Challenges and perspectives on liposome VADS
Chapter 13. Liposomes as DNA, mRNA and oligonucleotide delivery vectors
13.1. Introduction to nucleic acids delivery
13.2. Cationic liposomes
13.3. Conclusions and future perspective
Chapter 14. Liposomes for drug delivery by localized routes of administration
14.1. Introduction
14.2. Lung delivery
14.3. Intra-articular delivery
14.4. Ocular delivery
14.5. Vaginal delivery
14.6. Dermal delivery
14.7. Nasal delivery
14.8. Periodontal delivery
14.9. Intratumoral administration
14.10. Summary
Chapter 15. Liposomes for infectious diseases
15.1. Introduction-infectious diseases. Definition, categories and general treatment options
15.2. Strategies/mechanisms of liposome applications to treat infectious diseases
15.3. Liposomes for treatment of bacterial infections
15.4. Liposomes against fungal infections
15.5. Liposomes against virus infections
15.6. Liposomes against parasite infections
15.7. Clinical trials and products of liposomes for treatment of IDs
Chapter 16. Liposomes for drug delivery via biomaterials
16.1. Introduction
16.2. Liposomes and bone scaffolds
16.3. Liposomes and drug—Eluting stents
16.4. Liposomes and implants for treatment of infections
16.5. Liposomes integrated in implants for antitumor therapy
16.6. Liposomes integrated in implants for wound healing/dressing
16.7. Clinical studies
16.8. Summary
Chapter 17. Liposomes for delivery of substances for other (non-therapeutic) applications
17.1. Liposomes for non-therapeutic applications introduction
17.2. Concluding remarks
Chapter 18. Conventional methods for preparing liposomes of various types (MLVs, LUVs, SUVs): What, where, how and when
18.1. Introduction
18.2. Mechanism of liposome formation
18.3. Passive and active drug loading approaches
18.4. General drug loading approaches
18.5. Conventional methods for the preparation of phospholipid vesicles
18.6. Conclusions
Chapter 19. Size reduction, purification, sterilization and storage/packaging of liposomes
19.1. Introduction
19.2. Liposome sizing
19.3. Liposome purification
19.4. Sterilization
19.5. Packaging and storage
19.6. Summary
Chapter 20. Methods for preparation of giant liposomes: Conventional methods; modified electro-techniques
20.1. Introduction
20.2. Method of preparation of giant liposomes
20.3. Morphological modulation in giant liposomes
20.4. Potential of the above discussed methods to comply with regulatory guidelines for liposome products
20.5. Applications of giant liposomes in drug delivery
20.6. Conclusion and future direction
Chapter 21. Microfluidic methods for liposome formation
21.1. Introduction
21.2. Microfluidic mixing
21.3. Microfluidic preparation of liposomes
21.4. Microfluidic for advancing clinical applications
21.5. Concluding remarks
Chapter 22. Supercritical fluid methods for liposome production and sterilization
22.1. Introduction
22.2. Theoretical basis of methods
22.3. Supercritical fluids to produce liposomes
22.4. Supercritical fluids for the sterilization of liposomes
22.5. Supercritical fluids for the production and the sterilization of liposomes in a one step process
22.6. Potential of the method to comply with regulations guidelines for liposome products
22.7. Comparison to other novel methods
22.8. Conclusion
Chapter 23. Design of experiment approaches for liposome property optimization
23.1. Introduction
23.2. Definitions
23.3. The critical quality attributes (CQAs)
23.4. The critical material attributes (CMAs)
23.5. The critical process parameters (CPPs)
23.6. Application of DoE in liposome development
23.7. Factorial and fractional factorial designs
23.8. Box-Behnken design
23.9. Plackett Burman design
23.10. Central composite design
23.11. Response surface methodology (RSM)
23.12. Taguchi design
23.13. Challenges and future perspectives
23.14. Conclusions
Chapter 24. Development of generic liposome products for drug delivery
24.1. Introduction
24.2. Development of generic liposome formulation
24.3. Regulatory considerations for liposomal products
24.4. General considerations for the design of a liposomal formulation
24.5. Manufacturing process
24.6. Methods of drug loading
24.7. Processing of developed liposomes
24.8. Testing/analysis of liposomal formulations
24.9. Conclusion
Chapter 25. Success stories, final remarks and directions of the field
25.1. Conclusions – the current state of liposomes for drug delivery
25.2. Remaining challenges and future perspectives
25.3. Summary
Index

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Liposomes in Drug Delivery

What, Where, How and When to deliver

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Sophia G. Antimisiaris