liposome drug delivery system

LIPOSOMAL DRUG DELIVERY LIPOSOMAL DRUG DELIVERY SYSTEMSYSTEM

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LIPOSOMESLIPOSOMES

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ADVANTAGES ADVANTAGES

1) Effective encapsulation of both small and large 1) Effective encapsulation of both small and large molecules with a wide range of hydrophobicity levels and molecules with a wide range of hydrophobicity levels and Pk.Pk.

2) Prolonging and targeting release of therapeutic agents 2) Prolonging and targeting release of therapeutic agents by modification of liposome surface by modification of liposome surface

3) Minimizing clinical drug dose and reducing toxicity 3) Minimizing clinical drug dose and reducing toxicity effectseffects

4 Increased stability via encapsulation 4 Increased stability via encapsulation


PhospholipidsPhospholipids


Classification of liposomesClassification of liposomes

Structural parameters:Structural parameters: Multi lamellar vesicles.Multi lamellar vesicles. Oligo lamellar vesicles.Oligo lamellar vesicles. Unilamellar vesicles.Unilamellar vesicles. Small unilamellar vesicles.Small unilamellar vesicles. Large uni lamellar vesicles.Large uni lamellar vesicles. Multi vesicular vesicles.Multi vesicular vesicles.


METHOD OF PREPARATION:METHOD OF PREPARATION:

Single or oligo lamellar vesicles by REV.Single or oligo lamellar vesicles by REV.

Multi lamellar vesicles by REV.Multi lamellar vesicles by REV.

Vesicles prepared by extrusion method.Vesicles prepared by extrusion method.

Dehydration method.Dehydration method.


BASED ON COMPOSITION AND APPLICATION:BASED ON COMPOSITION AND APPLICATION:

Conventional liposomesConventional liposomes

Fusogenic liposomes. Fusogenic liposomes.

Long circulatory liposomesLong circulatory liposomes

Ph sensitive liposomes.Ph sensitive liposomes.

Cationic liposomes.Cationic liposomes.

Immuno liposomeImmuno liposome . .


CLASSIFICATIONCLASSIFICATION

METHOD OF LIPOSOMS PREPARATIONMETHOD OF LIPOSOMS PREPARATION

Passive loading active loadingPassive loading active loading

mechanical dispersion methodmechanical dispersion method solvent dispersion methodsolvent dispersion method detergent removal methoddetergent removal method


Mechanical dispersion methodsMechanical dispersion methods

lipid film hydration by hand shaking, lipid film hydration by hand shaking, non handshaking method. non handshaking method.

micro emulsification.micro emulsification. french pressure.french pressure. membrane extrusion.membrane extrusion. dried reconstituted.dried reconstituted. freeze-thawed.freeze-thawed.


DETERGENT REMOVAL METHOD:DETERGENT REMOVAL METHOD:

Detergent removal from mixed micelles.Detergent removal from mixed micelles.

Dialysis.Dialysis.

Column chromatography.Column chromatography.

Dilution.Dilution.


Solvent dispersion methods:Solvent dispersion methods:

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


MATERIALS USED FOR MATERIALS USED FOR PREPARATION OF LIPOSOMEPREPARATION OF LIPOSOME

1.Natural phospholipids1.Natural phospholipids

2.Synthetic phospholipids2.Synthetic phospholipids

3. Sphingolipids3. Sphingolipids

4. Glycosphingolipids4. Glycosphingolipids

5.Steroid5.Steroid

6. Polymeric material6. Polymeric material


Thin film hydration using hand Thin film hydration using hand shaking &non shaking methodshaking &non shaking method


French pressure cellFrench pressure cell


Sonication methodSonication method


Membrane extrusion methodMembrane extrusion method


Freeze taw liposomes & dried Freeze taw liposomes & dried reconstituted vesiclesreconstituted vesicles


Ethanol &ether injection methodEthanol &ether injection method


Reverse phase evaporation Reverse phase evaporation vesiclesvesicles


ACTIVE LOADING TECHNIQUE


DETERGENT REMOVAL MEHODSDETERGENT REMOVAL MEHODS

STAGE:1STAGE:1

At low concentrations Detergent

Lipid vesicular Lipid Water

STAGE:2

Size of vesicles

Critical detergent concentrations Membrane structure is unstable

Transforms gradually into micelles

STAGE:3

All Lipids exists in mixed micelle Form


DIALYSISDIALYSISDetergents High CMC

Removal is facilitated

Egg Pc + Sodium cholate dialysis Formation of vesicles


Stealth LiposomesStealth Liposomes

Major problem in use of liposomes for Major problem in use of liposomes for delivery of drug by injection in to blood delivery of drug by injection in to blood stream is the specific uptake of the stream is the specific uptake of the liposome by reticuloendothelial system .liposome by reticuloendothelial system .

avoid the uptake by the RES are called avoid the uptake by the RES are called stealth liposomes.stealth liposomes.


CHACTERIZATION OF CHACTERIZATION OF LIPOSOMESLIPOSOMES

Internal volume.Internal volume.

Encapsulation efficiency.Encapsulation efficiency.

Lamellarisity.Lamellarisity.

Size & size distribution..Size & size distribution..

Phase behaviour of liposomesPhase behaviour of liposomes


Therapeutic applicationTherapeutic application

Liposome as drug/protein delivery vehicles.Liposome as drug/protein delivery vehicles.Liposomes in anti microbial ,anti fungalLiposomes in anti microbial ,anti fungal anti viral therapy.anti viral therapy.Liposome in tumour therapy.Liposome in tumour therapy.Liposomes in gene delivery.Liposomes in gene delivery.Liposomes in immunology.Liposomes in immunology.Liposomes as radiopharmaceutical and Liposomes as radiopharmaceutical and

radiodiagnostic carriers.radiodiagnostic carriers.Liposoms in cosmetics and dermatology.Liposoms in cosmetics and dermatology.Liposomes in bioreactor technology.Liposomes in bioreactor technology.


REFERENSESREFERENSES REFERNCES:REFERNCES:Alpes H., Allmann K., Plattner H., Reichert J., Rick R. and Schulz S. (1986). Alpes H., Allmann K., Plattner H., Reichert J., Rick R. and Schulz S. (1986). Biochim.Biochim.Biophys. Acta. Biophys. Acta. 862862: 294.: 294.Bangham A.D., Standish M.M. and Watlins J.C. (1965). Bangham A.D., Standish M.M. and Watlins J.C. (1965). J. Mol. Biol. J. Mol. Biol. 1313: 238.: 238.Bangham A.D., Hill M.W. and Miller N.G.A. (1974). In: Methods in Membrane BiologyBangham 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.(Koln N.D., ed.) Plenum. N.Y., Vol.1, p.l.Batzri S. and Korn E.D. (1973). Batzri S. and Korn E.D. (1973). Biochim. Biophy. ActaBiochim. Biophy. Acta. . 298298: 1015.: 1015.Cestaro B., Pistolesi E., Hershkowitz N. and Galt S. (1982). Cestaro B., Pistolesi E., Hershkowitz N. and Galt S. (1982). Biochim. Biophys. ActaBiochim. Biophys. Acta. . 685685::Cullis R.P., Hope M.J., Bally M.B., Madden T.D. and Janoff AS. (1987). In: 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.) Liposomes from Biophysics to Therapeutics (Ostro M. J., Ed.) Marcel Dekker, N.Y., Marcel Dekker, N.Y., Chapter Chapter Deamer D. and Bangham A.D. (1976). Deamer D. and Bangham A.D. (1976). Biochim. Biophys. Acta. Biochim. Biophys. Acta. 443443: 629.: 629.Enoch H.G. and Strittmatter P. (1979). Enoch H.G. and Strittmatter P. (1979). Proc. Natl. Acad. Sci. Proc. Natl. Acad. Sci. USA. USA. 7676: 145.: 145.Fiona J., James A., Hayward A. and Chapman D. (1987). Fiona J., James A., Hayward A. and Chapman D. (1987). Biochim. Biophys. Biochim. Biophys. ActaActa.341..341.Friese J. (1984). In: Liposome Technology (Gregoriadis G., ed.) CRC Press, Florida,Friese J. (1984). In: Liposome Technology (Gregoriadis G., ed.) CRC Press, Florida,


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