1. Liposome: Novel Drug Delivery System Jignesh Patel M. Pharm.(sem-3) NPC,visnagar

3. What is a liposome? Liposomes are spherical self-closed structures, composed of curved lipid bilayers, which enclose part of the surrounding solvent into their interior. The size of a liposome ranges from some 20 nm up to several micrometers and they may be composed of one or several concentric membranes, each with a thickness of about 4 nm. Liposomes possess unique properties owing to the amphiphilic character of the lipids, which make them suitable for drug delivery. Formation of such a typical structural configuration is attributed to the amphiphilic character of phospholipids. When the letter are dispersed in excess of an aqueous phase, hydration of the polar head groups of the lipid results in a heterogeneous mixture of closed structures.

6. Size determined by methods: Sonication: SUV Smaller than 100 nm diameter Extrusion: LUV (Size depends on the filters) 100 nm—1 µm diameter Evaporation: MUV Larger than 1 µm diameter

8. Phospholipids: Polar Head Groups Three carbon glycerol

10. Preparation of liposomes:

18. Modes of liposome/cell interaction: Adsorption Endocytosis Fusion Lipid transfer

19. Uses of liposomes: Chelation therapy for treatment of heavy metal poisoning Enzyme replacement Diagnostic imaging of tumors Study of membranes Cosmetics Drug Delivery

21. Protection Decrease harmful side effects Pharmokinetics - efficacy and toxicity Changes the absorbance and biodistribution Change where drug accumulates in the body Protects drug Deliver drug in desired form Multidrug resistance Why use liposomes in drug delivery?

22. Release Affect the time in which the drug is released Prolong time -increase duration of action and decrease administration Dependent on drug and liposome properties Liposome composition, pH and osmotic gradient, and environment Why use liposomes in drug delivery?

23. Liposomes help improve: Therapeutic index Rapid metabolism Unfavorable pharmokinetics Low solubility Lack of stability Irritation

25. Current liposomal drug preparations: Type of Agents Examples Anticancer Drugs Anti bacterial Antiviral DNA material Enzymes Radionuclide Fungicides Vaccines Malaria merozoite, Malaria sporozoite Hepatitis B antigen, Rabies virus glycoprotein Amphotericin B In-111*, Tc-99m Hexosaminidase A Glucocerebrosidase, Peroxidase Duanorubicin, Doxorubicin, Epirubicin Methotrexate, Cisplatin*, Cytarabin Triclosan, Clindamycin hydrochloride, Ampicillin, peperacillin, rifamicin AZT cDNA - CFTR

26. No decrease in effectiveness of drug against fungi Liposomal formulation of AmB: Decrease in toxicity Exact Mechanism of liposomes not understood Cholesterol - only few %moles Phospholipid: AmB ratio Diffusion Lipid transfer AmB Lipid

28. Possibility of new side effects Problems continued Efficacy

29. Studies with insulin show that liposomes may be an effective way to package proteins and peptides for use Clinical Trials for several liposomal formulations More studies on the manipulation of liposomes Future

30. References Journals Allen, Theresa M. "Liposomal Drug Formulations: Rationale for Development and What We Can Expect for the Future." Drugs 56: 747-756, 1998. Allen, Theresa M. "Long-circulating (sterically stabilized) liposomes for targeted drug delivery ." TiPs 15: 214-219, 1994. Allen, Theresa M. "Opportunities in Drug Delivery." Drugs 54 Suppl. 4: 8-14, 1997 Janknegt, Robert. "Liposomal and Lipid Formulations of Amphotericin B." Clinical Pharmacokinetics. 23(4): 279-291, 1992. Kim, Anna et al. "Pharmacodynamics of insulin in polyethylene glycol-coated liposomes." International Journal of Pharmaceutics. 180: 75-81, 1999. Quilitz, Rod. "Oncology Pharmacotherapy: The Use of Lipid Formulations of Amphotericin B in Cancer Patients." Cancer Control. 5:439-449, 1998. Ranade, Vasant V. "Drug Delivery Systems: Site-Specific Drug Delivery Using Liposomes as Carriers." Pharmacology. 29: 685-694, 1989. Storm, Gert and Daan J.A. Crommelin. "Liposomes:quo vadi?" PSTT 1: 19-31, 1998. Taylor, KMG and JM Newton. "Liposomes as a vecicle for drug delivery." British Journal of Hospital Medicine. 51: 55-59, 1994

31. Websites James, John S. "Doxil Approved for KS." www.immunet. org.imminet/atn.nsf/page/a-235-03. Wasan, Ellen. "Targeted Gene Transfer." Member.tripod.com/~rrishna/lipos1.html "Introduction to Controlled Drug Delivery Systems." www5.bae.ncsu.edu/bae/reearch/blak… k/otherprojects/drugDeliver_97/ http://www. Mssm.edu/medicine/thrombosis/phosphol.html "Doxorubicin." http://tirgan.com/adria.htm "Clinical Pharmacology Online." http://www.cponline.gsm.com/scripts/fullmono/showmono. "Drugstore.com" http://www.drugstore.com/pharmacy/prices/Amphotec. "Sequus' Doxil Becomes First Liposome Product Approved In U.S." www.slip.net/~mcdavis/ database/doxor_1 "Liposomes." www.collabo.com/liposom0.htm Paustin, Timothy. “Cellular Membranes.”www.bact.wisc.edu/microtextbook/bacterialstructure/Membranegen.html www.cbc.umn.edu/~mwd/cell_www/chapter2/membrane.html#PHOSPHOLIPIDS Books Jones, Macolm N. and Chapman, David. Micelles, Monolayers and Biomembranes . Wiley-Liss. New York (1995). Garrett, R. and Grisham C. Biochemistry , 2 nd ed. Saunders Colleges Publishing. New York (1999). 264.