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Liposome: Novel Drug Delivery System Jignesh Patel M. Pharm.(sem-3) NPC,visnagar
[object Object]
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.
What is a liposome? ,[object Object],Hydrophilic Hydrophobic
Fundamental   properties:  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
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
Materials used for preparation: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Phospholipids: Polar Head Groups Three carbon glycerol
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],3D picture of a Phospholipid
Preparation   of liposomes:
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object]
Methods to check the morphology of liposomes: ,[object Object],[object Object]
Methods to control vesicle size of liposomes:   ,[object Object],[object Object],[object Object],[object Object]
Characterization   of liposomes: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
Classes of liposomes: ,[object Object],[object Object],[object Object],Cationic
Modes   of liposome/cell interaction:   Adsorption  Endocytosis Fusion Lipid transfer
Uses of liposomes: Chelation therapy for treatment of heavy metal  poisoning Enzyme replacement Diagnostic imaging of tumors Study of membranes Cosmetics Drug Delivery
Why   use liposomes in  drug delivery? ,[object Object],[object Object],[object Object],[object Object],Physical:  temperature or pH sensitive liposomes  Drug targeting
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?
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?
Liposomes help improve: Therapeutic index Rapid metabolism Unfavorable pharmokinetics Low solubility Lack of stability Irritation
Custom design: ,[object Object],[object Object],[object Object],[object Object]
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
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
Problems with liposomal preparations of drugs: Cost   ,[object Object],[object Object],[object Object],Lack long term stability (short shelf life) Freeze dry and pH adjustment Low “Pay Load” - poor encapsulation Physical and chemical instability   Polar drugs and drugs without opposite charge Modifications
Possibility of new side effects Problems   continued Efficacy
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
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
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.
[object Object]

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Presentation1

  • 1. Liposome: Novel Drug Delivery System Jignesh Patel M. Pharm.(sem-3) NPC,visnagar
  • 2.
  • 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.
  • 4.
  • 5.
  • 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
  • 7.
  • 8. Phospholipids: Polar Head Groups Three carbon glycerol
  • 9.
  • 10. Preparation of liposomes:
  • 11.
  • 12.
  • 13.
  • 14.
  • 15.
  • 16.
  • 17.
  • 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
  • 20.
  • 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
  • 24.
  • 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
  • 27.
  • 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.
  • 32.

Editor's Notes

  1. Depend on the number of bilayers liposomes can be divided into multilamellar and unilamellar vesicles. According to the size unilamellar vesicles can be further divided into SUV LUV, GUV. They are prepared by different methods. SUV smaller than 100 nm diameter by sonication, LUV 100 nm to 1micro meter can be prepared by extrusion GUV larger than 1 micro meter can be prepared by evaporation.
  2. SUV are typically 15-30nm in diameter while LUV range from 100-200nm or larger. LUV are stable on storage, however, SUV will spontaneously fuse when they drop below the phase transition temperature of the lipid forming the vesicle.
  3. There are many methods to characterize the liposomes. To characterize the morphology of liposomes EM LS are the most common method. I will shortly discribe EM and LS here the details can be found in literature.