Liposomes are the first nano-drug delivery systems that have been successfully translated into real-time clinical applications. These closed bilayer phospholipid vesicles have witnessed many technical advances in recent years since their first development in 1965.

1. Thermosensitive liposomes
Sujeet Singh (NK20MSPM697)
M.S.(Pharm)-Pharmaceutics
Pallabh Datta
Niper Kolkata

2. Topics
• Project Description
• Salient features of Liposomes
• Structure of Liposomes
• First research area
• Classification of Liposomes
• Preparative methodology of Liposomes
• Structure of Phospholipid bilayer
• Composition of liposomes
• Application
• Therapeutic areas covered by liposome-based products
• Liposomes present under different phases of clinical trial investigation
• Application
• Drawbacks
• Conclusion

3. Project Description
Objective
• The opinion of liposomal drug delivery system has revolutionized the pharmaceutical field.
• The name of liposome is derived from two Greek words: "Lipos" means fat, and "Soma" means body.
• The concept of liposomes was first described by Alec Bangham in the 1960s.
• Liposomes, at the beginning called smectic mesophases, are unilamellar or
multilamellar spherical vesicles, specially containing phospholipids from plant or animal sources
• Liposomes are self-assembled closed spherical structures composed of one or more concentric curved
Phospholipid bilayer.
• They range in size from 20 nm to many microns, because of the amphiphilicity of the lipids used in
liposomes.
• The amphiphilic phospholipid bilayer of liposome could be very similar to mammalian cell membrane,
which bring in the effective interaction between liposome and cellular membrane
and subsequent effective cell uptake.

4. Salient features of liposomes
• Liposomes are composed of natural lipid.
• Simple Microscopic vesicles
• Biologically inert, biodegradable, and weakly immunogenic.
• Passive targeting to RES
• Avoid to RES by PEGylation
• Increased plasma circulation and increased half life
• Active targeting
• Least toxic
• Enhanced efficacy

5. Structure of Liposomes

6. First research area
•In 1978, Yatvin suggested for the first time the use
of temperature sensitive liposomes (TSLs) (i.e., liposomes that release the
encapsulated drug in response to thermal.
•The simple concept was to administer this liposomal drug systemically, and
then expose only the tissue region
where drug delivery is intended to hyperthermia for targeting the drug to tumors or
local infections.
•They proposed to use slightly higher temperature (42–44°C) than normal body
temperature (37°C) to target drug delivery.

7. First research area Cont.
•This first TSL formulation used the two Phospholipids dipalmitoyl phosphatidylcholine
(DPPC) and distearoyl phosphatidylcholine (DSPC) to make liposomes sensitive to heat.
•DPPC and DSPC have “liquid‐ crystalline transition temperatures (Tm)” of 41 and 54°C,
respectively

8. Classification of liposomes
• Liposomes can be Classified in different ways-
1. Based on Charge
2. Based on the diameter and the number of lipid bilayer
• Liposomes can be negatively charged, neutral, or positively charged by the
addition of other materials at a certain pH environment.
• For the delivery of nucleic acids, positively charged liposomes containing
cationic lipids , such as DOTAP (Dioleoyl trimethyl ammonium propane).

9. Cont.

10. Preparative methodology of Liposomes

11. Thin-film hydration
• Thin-film hydration is the most widely used preparation method for
liposomes.
• In which, lipid components with or without a drug are dissolved in an
organic solvent.
• The solvent will be evaporated by rotary evaporation followed by
rehydration of the film in an aqueous solvent.
• Techniques like membrane extrusion, sonication, homogenization and
freeze-thawing are being employed to control the size and size
distribution.

12. Structure of Phospholipid Bilayer

13. Composition of Liposomes
• Phospholipid and Cholesterol are the main component of Liposomes.
Phospholipid-
• Fatty substance
• Major structural component of cell wall and biological membrane
• Amphipathic Molecule
• One Hydrophilic head group and two hydrophobic tail group
• Having Phosphatidyl moiety in tail group and choline, Ethanolamine and
Serine moiety in head group.
• Phosphatidylcholine(PC) is the most common natural Phospholipid

14. Cont.

16. Application
•Liposomes are extensively used in-
•Drug delivery
•Gene Delivery
•Vaccine Delivery
•Molecular imaging
•Cosmetics and food industry

17. Therapeutic areas covered by liposome-based products

18. Liposomes present under different phases of
clinical trial investigation

19. Advantages
• Higher efficacy and therapeutic index
• Provide selective passive targeting to tumor tissue
• Control over Pharmacokinetic and Pharmacodynamic properties
• Improved bioavailability
• Least toxicity
• Best Suited for Controlled release
• Highly flexible and Non immunogenic
• Suitable for delivery of hydrophilic, hydrophobic and Amphipathic drugs

20. Drawbacks
•High production cost
•Oxidation and hydrolysis of Phospholipids
•Leakage of Encapsulated drug
•Low Solubility

21. Conclusion
• Liposomes made their successful entry into the market in 1995 with the
development of the PEGylated liposomal formulation Doxil®.
• These delivery systems, have been explored for various diseases ranging from
cancer treatment to pain management.
• “liposomes are successfully utilized in all imaginable drug delivery approaches
and their use to solve various biomedical problems is steadily increasing”.
• Liposomes “present the prototype of all nanoscale drug delivery.
• The history of over 40 years of Liposome technology should be heeded by new
investigators in the emerging field of pharmaceutical and biomedical
nanotechnology”.
• Different types of liposomes, e.g., PEGylated liposomes (Lipodox), temperature
sensitive liposomes (ThermoDox), cationic liposomes (EndoTAG-1) and
liposomal vaccines (Epaxal and Inflexal V), demonstrate the intense research on
liposomes.

22. Appendix
• https://www.researchgate.net/figure/Lipid-bilayer-structure-A-Molecular-
composition-of-phospholipid-and-B-cell-membrane_fig1_281864200.
• https://www.creative-biolabs.com/lipid-based-delivery/the-concept-and-
history-of-liposomes.htm
• file:///C:/Users/admin/Downloads/pharmaceutics-09-00012-v2.pdf.
• https://link.springer.com/protocol/10.1007/978-1-4939-6591-5_1
• https://pubmed.ncbi.nlm.nih.gov/28346375/
• https://www.researchgate.net/figure/e-Structure-of-cholesterol-with-the-
numbering-of-the-carbon-atoms_fig1_328067177.
• https://eatbettermovemore.org/role-of-cholesterol-in-lipid-bilayer/.