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Liposome drug delivary system, PHARMACOKINETICS,manipal,pharmaceutics,gpat,powerpoint presentations,niper,pharmacy material,pharmacy ppts,entrance exam materials,physical pharmacy,chronopharmacokinetics
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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
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PhospholipidsPhospholipids
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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.
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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.
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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 . .
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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
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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.
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DETERGENT REMOVAL METHOD:DETERGENT REMOVAL METHOD:
Detergent removal from mixed micelles.Detergent removal from mixed micelles.
Dialysis.Dialysis.
Column chromatography.Column chromatography.
Dilution.Dilution.
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Solvent dispersion methods:Solvent dispersion methods:
Ethanol injection.Ethanol injection. Ether injection.Ether injection. Double emulsion. Double emulsion. Reverse phase evaporation.Reverse phase evaporation.
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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
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Thin film hydration using hand Thin film hydration using hand shaking &non shaking methodshaking &non shaking method
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French pressure cellFrench pressure cell
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Sonication methodSonication method
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Membrane extrusion methodMembrane extrusion method
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Freeze taw liposomes & dried Freeze taw liposomes & dried reconstituted vesiclesreconstituted vesicles
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Ethanol ðer injection methodEthanol ðer injection method
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Reverse phase evaporation Reverse phase evaporation vesiclesvesicles
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ACTIVE LOADING TECHNIQUE
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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
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DIALYSISDIALYSISDetergents High CMC
Removal is facilitated
Egg Pc + Sodium cholate dialysis Formation of vesicles
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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.
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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
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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.
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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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