Liposomes

Liposomes

1. Types, preparation and evaluations of liposomes 1 Presented by, Mr. Akash U. Thakur M. Pharm II nd sem Dept. of Pharmaceutics Guide, Dr. N. M. Mahajan Head, Dept. of Pharmaceutics DBCOP, Besa, Nagpur.

2. Contents Introduction Structure of liposome Advantages Disadvantages Types of liposomes Method of liposome preparation Characterization of liposomes Application of liposomes References 2

3. Liposomes Liposomes first described by Dr . A. D. Bingham in 1965 . The Liposomes are the micro-particular drug carrier one or more concentric phospholipids bi-layer separated by aqueous buffer compartments known as “ Liposomes ”.. Liposomes is Greek words means ‘Lipo ’ mean ‘Fat’ and ‘ Somes ’ mean ‘Body ’. Their diameter ranges from 80nm to 100µm. 3

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5. Advantages Liposomes increased efficacy and therapeutic index of drug. Liposomes increased stability via. encapsulation. Provide selective passive targeting to tumour tissues. Improved pharmacokinetic effects (reduced elimination, increased circulation life time). Liposomes reduce the toxicity of the encapsulation. Facilitation of transport across membranes. 5

6. Disadvantages Low solubility in water. Sometimes phospholipid undergoes oxidation and hydrolysis like reaction. Production cost is high. 6

7. 1. Based on structural parameter MLV (Multi-lamellar large vesicles), OLV ( Oligo -lamellar vesicles), UV ( Uni -lamellar vesicles), SUV (Small uni -lamellar vesicles), MUV (Medium sized unilamellar vesicles), LUV (Large unilamellar vesicles), MV ( Multivesicular vesicles ). 7 Types of liposomes

8. 2. Based on method of liposome preparation REV (Single or O ligolamellar vesicles made by reverse phase evaporation method). MLV-REV (Multi-lamellar vesicles made by reverse phase evaporation method). SPLV (Stable P luri-lamellar vesicles). DRM (Dehydration rehydration method). 8

9. 3. Based upon composition and applications CL (Conventional liposomes), Fusogenic liposomes, pH sensitive liposomes, Cationic liposomes, Immuno-liposomes . 9

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11. 1. Mechanical dispersion methods. 11

12. Lipid film hydration by hand shaking 12 Fig. Multilaminar vesicles (MLVs) formed by hand shaking technique

13. 13 2. Solvent dispersion method

14. 14 Reverse phase evaporation vesicles

15. 3. Detergent removal methods 15 The conc. of detergent at which micelles are formed is called as CMC.

16. 16 Phospholipids in the form of either sonicated vesicles or as a dry film, at a molar ratio of 2:1 with deoxycholate form unilamellar vesicles of 100 nm on removal of deoxycholate by column chromatography. This could be achieved by passing the dispersion over a Sephadex G-25 column pre-saturated with constitutive lipids and pre-equilibrated with hydrating buffer. Column chromatography

17. Characterization of liposomes Physical characterization. Chemical characterization. 17

18. Physical characterization Sr. No. Characterization parameter Analytical methods / Instrument 1. Vesicle shape and surface morphology Electron Spectroscopy. 2. size and size distribution Electron microscopy. 3. Surface charge Free- flow electrophoresis. 4. Electrical surface potential and surface pH Zeta-potential. 5. Lamellarity X- ray scattering, 31 P-NMR, Freeze-electron microscopy. 6. Phase behaviour of liposomes Electron microscopy. 7. % of free drug Mini- coloumn centrifugation, ion-exchange chromatography, radio labeling. 8. Drug release Diffusion cell. 18

19. Chemical characterization Sr. No. Characterization parameter Analytical methods / Instrument 1. Phospholipid concentration HPLC 2. Cholesterol concentration Cholesterol O xidase assay and HPLC 3. Phospholipid peroxidation UV absorbance 4. Phospholipid hydrolysis, Cholesterol auto-oxidation HPLC and TLC 5. Osmolarity Osmomete r 19

20. In gene delivery. As drug delivery carriers. Enzyme replacement therapy. Liposomes in anti-viral / anti-microbial therapy. In multi drug resistance. In Tumour therapy. In Immunology. In Cosmetology. 20 Application of liposomes

21. Liposome i n gene delivery variety of physical and biological methods have been developed for transferring gene into cells. The most widely used type of vehicles for gene delivery are viral and non-viral. The non-viral vector systems, liposomes and lipid complexes especially engineered liposome such as pH sensitive liposomes, cationic liposomes, fusogenic liposome, genosomes , lipoplex , and l ipopolyplex have been extensively investigated for their gene delivery potential. However, most of the commercially available non-viral gene vectors used for transfection are cationic liposomes-DNA complexes. 21

22. 22 Fig. Liposome in gene delivery

23. Liposome a s drug delivery carriers Several modes of drug delivery applications have been proposed for the liposomal system for some of the pathogen caused diseases. The major ones are - Enhanced drug solubility. E.g. Amphotericin B. Protection of sensitive drug molecules. E.g. DNA, RNA, Ribosomes . Enhanced intracellular uptake. E.g. Anticancer drugs, Antiviral and Antimicrobial drugs. 23

24. Liposome in tumour therapy Most of the medical application of liposomes have reached the preclinical and clinical stages are in cancer treatments. It has been demonstrated that small and stable liposomes can passively target several different tumour because they can circulates for prolonged times. Targeting liposomes can be using in different ways - Natural targeting of liposomes, Use of long circulatory, Use of ligand mediated targeting. 24

25. Liposome in Cosmetology and dermatology In early studies, liposomes containing stratum corneum lipids have been tested in order to enable better skin penetration. Two mechanism for enhanced topical localization or targeting of liposome encapsulated bioactives . The transepidermal pathway. (skin layers) The transfollicular pathway. (hair follicles and glands) Liposome based on anti-aging formulations (e.g. creams, lotions, gels and hydrogels) have been formulated and launched in the cosmetic market by L oreal in 1986. Liposomal preparation reduce the roughness because of its interaction with the intracellular lipid resulting in skin softening and smoothing. 25

26. Marketed products 26

27. References S. P. Vyas & R. K. Khar , “ Targeted & Controlled Drug Delivery Novel Carrier Systems” First edition 2002, CBS Publishers & Distributors Pvt. Ltd., Page no. 173-205. www.wikipedia.com 27

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29. ANY QUESTIONS…? 29