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“LIPOSOMES- A NOVEL VESSICULAR CARRIER”

Presented ByMr. Bhosale Pramod

Motiram

M. Pharm (SEM- I)Pharmaceutics

Roll No-02

Guided By-Prof. A. W. Ambekar

M. Pharm. Pharmaceutics

.

A Seminar on

DR.VITHALRAO VIKHE PATIL FOUNDATION’S COLLEGE OF PHARMACY, AHMEDNAGAR.

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Introduction Advantages & Disadvantages Mechanism of liposomes action Classification Types Of Liposomes Method of Liposome Preparation Evalution of Liposomes Applications Recent Advances Some marketed Preparation

CONTENTS

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Liposomes are simple microscopic , concentric bi-layered vesicles in which an aqueous

volume is entirely enclosed by a membranous lipid bi-layer mainly composed of

phospholipids and cholesterol.

Liposomes were discovered by Bhangam and co-workers in 1960’s in England.

The size of a liposome is upto 20 nm

Liposomes are the drug carrier loaded with great variety of molecules such as small drug

molecules, proteins, nucleotides & even plasmids.

Liposomes can be produced from cholesterols, non toxic

surfactants,sphingolipids,glycolipids,long chain fatty acids & even membrane proteins.

INTRODUCTION

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General structure of liposome

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ADVANTAGES: Biocompatibility and Biodegradability. Easy to manufacture. Targeted drug delivery Prolonged circulation in stealth mode Able to protect encapsulated drug from degradation.

DISADVANTAGES: Poor stability High manufacturing cost Poor loading capacity Challenging sterilization Poor reproducibility

Advantages & Disadvantages

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Mechanisms by which liposomes act

Outside of the cell.

Liposome

Inside of cell.

Inside of cell.

Drug releasing into cell

Cell membraneCell

membrane

Phospholipids of liposome are incorporated into cell membrane

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Classification BASED ON STRUCTURE : Multi-lamellar large vesicles (>0.5 µm) MLV Oligo-lamellar vesicles (0.1 – 1µm) OLV Uni-lamellar vesicles ( All size ranges) UV Small uni-lamellar vesicles (20 – 100 nm) SUV Medium size uni-lamellar vesicles (>100 nm) MUV Large uni-lamellar vesicles (>100 nm) LUV Giant uni-lamellar vesicles (>1 µm) GUV Multi-vesicular vesicles (>1 µm) MV

BAESD ON LIPOSOMAL FORMATION: Reverse phase evaporation REV Multi-lamellar vesicle by REV MLV-REV Stable plurilamellar vesicle SPLV Frozen and thawed MLV FATLV Vesicles prepared by extrusion techniques VET Dried reconstituted vesicles DRV

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There are two type of liposomes based on their structure.

a) Unilamellar liposomes: Unilamellar vesicles has a single phospho-lipid bilayer

sphere enclosing aqueous solution.

b) Multilamellar Liposomes: Multilamellar vesicles have onion structure. Typically,

several Unilamellar vesicles will form one inside the other in diminishing size,

creating a multilamellar structure of concentric phospholipid spheres separated by

layers of water.

Types of Liposomes

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a) Handshaking Method-

b) Sonication Method-

Methods of Liposomes Preparation

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There are two sonication techniques:

i) Probe Sonication

ii) Bath Sonicator

c) Reverse Phase Evaporation Method:-Lipid organic solvent aqueous solution

mix

sonicate

formation of w/o emulsion

evaporate to remove the organic solvent

Lipids form a phospholipid bilayer

vigorous shaking

water droplets collapse

formation of LUV’s. 

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d) Freeze Dried Rehydration Method:- It is obtained from Pre-formed liposomes. Small macromolecule can be achieved in this. During dehydration, lipid bilayer & material are

encapsulated in liposomes. They are braught in closed contact. Aqueous phase should be added in small portion to

get Rehydration Method.

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Evaluation could be classified into three broadCategories,

1. Physical2. Chemical3. Biological parameters.

Techniques:- Microscopic Techniques1. Optical Microscopy2. Cryo-Transmission Electron Microscopy Techniques (cryo-TEM) Diffraction and Scattering Techniques Hydrodynamic Techniques

EVALUTION OF LIPOSOMES

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Formulation of antineoplastic drugs into liposomes will significantly enhances systemic

circulation time.

Decreased toxicity by reducing free drug levels in plasma.

Increased EPR (Enhanced permeability &retention effect).

Decreased cardio-toxicity of Doxorubicin by liposomal encapsulation.

Positively charged liposomes have enhanced immunogenic properties for vaccines and

hypersensitivity responses.

PEGylated liposomes are recent advancement in brain targeted drug delivery systems.

Liposomes used as drug carriers for efficient treatment of neuronal inflammation (Methyl

prednisolone) & others exhibited superior anti inflammatory activity than Other activity.

APPLICATIONS

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1) Liposomes in Cancer2) Sustain release Liposomes3) Liposomes in Gene Delivery4) Lipsomes for Protein & Peptide Delivery5) Liposome for Oral administration6) PH Sensitive Liposomes7) Antibody Mediated targeting liposomes

RECENT ADVANCES IN LIPOSOMES

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Brand Name Drug Category RouteDoxil Doxorubicin Anticancer Intravenous

Daunoxome Daunorubicin Anticancer Intravenous

Epaxel Hepatitis A vaccine

Protection against

Hepatitis

Subcutaneous

Elamax Lidocaine Local anesthetic Topical

Mikasome Amikacine Antibacterial Intravenous

SOME MARKETED PREPARATIONS

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Vyas S.P., Khar K.R. Trageted and Controlled drug delivery. CBS Publisher and distributors, New Delhi. 2002; 1;181,187.

Riaz.M. Liposomes preparation method pakisthan journal of pharmaceutical sciences. 1996; 19(1); 65-77.

Lipowsky R. Nature 1992; 349: 475–481. Lasic DD. Elsevier Amsterdam 1993;231.

Svetina S and B Zeks. Biophys Acta 1982; 44: 979–986.

Alving C. R. et al., Therapy of Leishmaniasis: Superior Efficacies of Liposome‐Encapsulated Drugs, Proc. Natl. Acad. Sci.

(USA),1978, 75, 2959–2963.

Lopez‐Berestein G. et al., Liposomal Amphotericin B for the treatment of Systemic Fungal Infections in Patients with

Cancer: A Preliminary Study, J. Infect. Dis., 1985, 151, 704–710.

Gregoriadis G. Genetic Vaccines: Strategies for Optimization, Pharm. Res., 1998, 15, 661–670.

Spanjer H. H., Scherphof G., Targetting of lactosylceramidecontaining liposomes to hepatocytes in vivo. Biochim

Biophys.Acta, 1983, 174, 40‐47.

Nicolau C., Legrand A., Grosse E., Liposomes as carriers for in vivo gene transfer and expression, Methods in

enzymology,1987, 149, 157‐176.

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REFERENCE

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THANK YOU…

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