Liposomes

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Presentation Transcript

Liposomes (Chapter- 2):

Liposomes (Chapter- 2) Novel Drug Delivery System- II Presentation by Abhishek Bagadiya Enrollment No.102100808006 M.Pharm Sem.-III Atmiya Institute of Pharmacy, Rajkot.

Pool of Contents:

Pool of Contents Introduction Definition Merits & Demerits Materials Classification Methods of Preparation

Introduction:

Introduction Liposomes were first produced in England in 1961 by Alec D. Bangham . The name liposome is derived from two Greek words 'Lipid‘ fat and 'Soma‘ body.

Definition:

Definition Liposomes are microscopic spheres made from fatty materials , predominantly phospholipids. Liposomes are made of molecules with hydrophilic and hydrophobic ends that form hollow spheres which can encapsulate water-soluble ingredients in their inner water space and oil-soluble ingredients in their phospholipid membranes that are made up of one or more concentric lipid bilayers , and range in size from 50 nanometers to several micrometers in diameter.

Merits:

Merits Enhancing its therapeutic efficacy (drug targeting, site-specific delivery). Protection of drug by encapsulation. Site avoidence effect. Immunological adjuvant Improved pharmacokinetic effects (reduced elimination, increased circulation life times). Flexibility to couple with site specific ligands to achieve active targeting. Biocompatible & Biodegradable.

Demerits:

Demerits Phospholipid on hydrolysis yields lysophospholipid and free fatty acid which results instability. On oxidation of lipid results instability. Oral adminisation is not possible. Expensive. RES uptake.

Classification:

Classification Composition and Application Structural Parameters Method of Preparation

Based on Composition and Application:

Based on Composition and Application Conventional liposomes (Neutral or Negatively charged phospholipid and cholesterol) Long-circulating liposomes ( 5-10% PEG) Cationic liposomes ( Cationic lipids with DOPE) Immunoliposomes Temp.-sensitive immunoliposomes pH-sensitive immunoliposomes ( using phospholipids such as PE or DOPE with OA)

Slide 10:

Conventional Long circulating

Slide 11:

Immuno Cationic

Based on Structural Parameters:

Based on Structural Parameters Multilamellar vesicles MLV (> 0.5µm) Oligolamellar vesicles OLV (0.1-1.0µm) Unilamellar vesicles UV (All size range) Small unilamellar vesicles SUV (20-100nm) Medium sized unilamellar vesicles MUV Large sized unilamellar vesicles LUV (>100nm) Giant unilamellar vesicles GUV (>1µm) Multivesicular vesicles MV (>1µm)

Slide 13:

Unilamellar Multilamellar

Based on Method of Preparation:

Based on Method of Preparation Reverse phase evaporation vesicles (REV) Stable plurilamellar vesicles (SPLV) Frozen and Thawed MLV (FTMLV) Vesicles prepared by extrusion method (VET) Dehydration- Rehydration method (DRV)

Materials:

Materials Phospholipids Natural Phospholipids: Phosphotidylcholine Phosphotidylserine Phosphotidylethanolamine Synthetic Phospholipids: Dipalmitoylphosphotidylcholine Distearoylphosphotidylcholine

Materials:

Materials Sphingolipids : Shingomyelin Glycosphingolipids : Gangliosides Steroids: Cholesterol Polymeric material : Lipids conjugated to diene , methacrylate & thiol group Charge-inducing lipids: Dioctadecyldimethyl ammonium bromide/chloride (DODAB/C) Other Substances: Stearylamine , Polyglycerol

Methods of Preparation:

Methods of Preparation

Passive loading technique:

Passive loading technique Sonication Microemulsification French pressure cell Membrane extrusion Dried reconstituted vesicles Freeze thawed liposome Ethanol injection Ether injection Reverse phase evaporation Stable plurilamellar vesicles Detergent removal Dialysis Column chromatography Dilution Mechanical dispersion Solvent dispersion Detergent removal

General Method of Preparation:

General Method of Preparation

Drying:

Drying An important step involved in the preparation of liposomes is the drying of the lipid. Large volume of organic solution of lipid is most easily dried in a rotary evaporator fitted with a cooling coil and thermostatically controlled water bath. Rapid evaporation of solvent is carried out by gentle warming (20-40 degrees) under reduced pressure (400- 700 mm Hg). Rapid rotation of the solvent containing flask increases the surface area for evaporation.

Slide 21:

In cases where sufficient vaccum is not attainable of if the concentration of lipid is purticularly high, it may difficult to remove the last traces of chloroform from the lipid film. Therefore it is recommended that after rotary evaporation, some further means of drying is required for complete dryness. Attachment of flask to the lyophilizer and overnight exposure to high vaccum is good method

Sonication method:

Sonication method

French pressure cell method:

French pressure cell method

Microemulsification:

Microemulsification

Dried reconstituted vesicles and Freeze thaw sonication:

Dried reconstituted vesicles and Freeze thaw sonication

Extrusion method:

Extrusion method

Ether injection method:

Ether injection method

Ethanol injection method:

Ethanol injection method

Reverse phase evaporation vesicles:

Reverse phase evaporation vesicles

Detergent removal method:

Detergent removal method In this method, the phospholipids are brought into intimate contact with the aqueous phase via the detergents which associate which associate with phospholipid molecules and serve to screen the hydrophobic portion of the molecules from water. The strucure formed as a result of this association are known as micelles. Their size and shape depend on chemical nature of the detergent, the concentration and other lipids are involved.

Slide 32:

Detergents are removed by Dialysis Column chromatography Adsorption on carriers

Active or remote loading technique:

Active or remote loading technique The membrane from lipid bilayer is in general impermeable to ions and larger hydrophilic molecules. Ion transport can be regulated by the ionophores while permeation of neutral and weakly hydrophobic molecules can be controlled by concentration gradients. Some weak acids or bases however. Can be transported trough the membrane due to various transmembrane gradients, such as electrical, ionic (pH) or specific salt (chemical potential) gradients.

Advantages active loading over passive loading:

Advantages active loading over passive loading A high encapsulation efficiency and capacity. A reduced leakage of the encapsulated compounds. “Bed side” loading of drugs thus limiting loss of retention of drugs by diffusion, or chemical degradation during storage. Flexibility for the use of constitutive lipids, as drug is loaded after the formation of carrier units. Avoidance of biological active compounds during preparation steps in the dispersion thus reducing safety hazards.

References:

References Sharma Shailesh , Sharma Neelam , Liposomes : A review. J. Pharm. Res. 2009;2(7):1163 -1167. Jain NK. Controlled and novel drug delivery. CBS Publishers & distributors; New Delhi: 2001. Vyas SP, Khar RK, Liposomes . Targeted & controlled drug delivery system. 1 st ed. CBS Publishers & distributors; New Delhi: 2002.

Slide 36:

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