LIPOSOMAL DRUG DELIVERY SYSTEM

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LIPOSOMES

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ADVANTAGES
1) Effective encapsulation of both small and large molecules with a wide range of hydrophobicity levels and Pk. 2) Prolonging and targeting release of therapeutic agents by modification of liposome surface

3) Minimizing clinical drug dose and reducing toxicity effects 4 Increased stability via encapsulation

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Phospholipids

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Classification of liposomes
Structural parameters:
Multi lamellar vesicles. Oligo lamellar vesicles. Unilamellar vesicles. Small unilamellar vesicles. Large uni lamellar vesicles. Multi vesicular vesicles.
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METHOD OF PREPARATION: Single or oligo lamellar vesicles by REV. Multi lamellar vesicles by REV. Vesicles prepared by extrusion method. Dehydration method.

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BASED ON COMPOSITION AND APPLICATION:

Conventional liposomes Fusogenic liposomes. Long circulatory liposomes Ph sensitive liposomes. Cationic liposomes. Immuno liposome .
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CLASSIFICATION
METHOD OF LIPOSOMS PREPARATION Passive loading active loading 

mechanical dispersion method  solvent dispersion method  detergent removal method
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Mechanical dispersion methods       lipid film hydration by hand shaking, non handshaking method. micro emulsification. french pressure. membrane extrusion. dried reconstituted. freezefreeze-thawed.

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DETERGENT REMOVAL METHOD: Detergent removal from mixed micelles. Dialysis. Column chromatography. Dilution.

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Solvent dispersion methods: 

  

Ethanol injection. Ether injection. Double emulsion. Reverse phase evaporation.

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MATERIALS USED FOR PREPARATION OF LIPOSOME
1.Natural phospholipids 2.Synthetic phospholipids 3. Sphingolipids 4. Glycosphingolipids 5.Steroid 6. Polymeric material

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Thin film hydration using hand shaking &non shaking method

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French pressure cell

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Sonication method

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Membrane extrusion method

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Freeze taw liposomes & dried reconstituted vesicles

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Ethanol &ether injection method

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Reverse phase evaporation vesicles

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ACTIVE LOADING TECHNIQUE

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DETERGENT REMOVAL MEHODS
STAGE:1
At low concentrations Detergent Lipid vesicular Lipid Water

Size of vesicles

STAGE:2
Critical detergent concentrations Membrane structure is unstable

Transforms gradually into micelles

STAGE:3
All Lipids exists in mixed micelle Form
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DIALYSIS
Detergents High CMC Removal is facilitated

Egg Pc + Sodium cholate

dialysis

Formation of vesicles

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Stealth Liposomes
Major problem in use of liposomes for delivery of drug by injection in to blood stream is the specific uptake of the liposome by reticuloendothelial system . avoid the uptake by the RES are called stealth liposomes.

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CHACTERIZATION OF LIPOSOMES
Internal volume. Encapsulation efficiency. Lamellarisity. Size & size distribution.. Phase behaviour of liposomes

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Therapeutic application 
Liposome as drug/protein delivery vehicles.  Liposomes in anti microbial ,anti fungal anti viral therapy.  Liposome in tumour therapy.  Liposomes in gene delivery.  Liposomes in immunology.  Liposomes as radiopharmaceutical and radiodiagnostic carriers.  Liposoms in cosmetics and dermatology.  Liposomes in bioreactor technology.
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REFERENSES
REFERNCES: Alpes H., Allmann K., Plattner H., Reichert J., Rick R. and Schulz S. (1986). Biochim. Biophys. Acta. 862: 294. 862: Bangham A.D., Standish M.M. and Watlins J.C. (1965). J. Mol. Biol. 13: 238. 13: Bangham A.D., Hill M.W. and Miller N.G.A. (1974). In: Methods in Membrane Biology (Koln N.D., ed.) Plenum. N.Y., Vol.1, p.l. Batzri S. and Korn E.D. (1973). Biochim. Biophy. Acta. 298: 1015. Acta. 298: Cestaro B., Pistolesi E., Hershkowitz N. and Galt S. (1982). Biochim. Biophys. Acta. Acta. 685: 685: Cullis R.P., Hope M.J., Bally M.B., Madden T.D. and Janoff AS. (1987). In: Liposomes from Biophysics to Therapeutics (Ostro M. J., Ed.) Marcel Dekker, N.Y., Chapter Deamer D. and Bangham A.D. (1976). Biochim. Biophys. Acta. 443: 629. 443: Enoch H.G. and Strittmatter P. (1979). Proc. Natl. Acad. Sci. USA. 76: 145. 76: Fiona J., James A., Hayward A. and Chapman D. (1987). Biochim. Biophys. Acta.341. Acta.341. Friese J. (1984). In: Liposome Technology (Gregoriadis G., ed.) CRC Press, Florida,

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