LIPOSOMES

PRESENTED BY
DEBASHISH GHOSE M.PHARM 2nd SEMESTER (PHARMACEUTICS) Regd.no:1008253022 COLLEGE OF PHARMACEUTICAL SCIENCES (BERHAMPUR)

CONTENT

Introduction
y Liposome have been widely considered as a potential drug

delivery system since 1st reported in 1965 by Bangham.

y liposome can be defined as simple microscopic vesicles in

which an aqueous volume is entirely enclosed by a bilayered membrane composed of lipid molecule.
y The molecule may be encapsulated in aqueous space or

intercalated into the lipid bi-layers

y Liposomes are discovered in the year 1960 and subsequently

became the most extensively explored drug delivery system However their predominance delivery and targeting has enable them to used as therapeutic tool in field life tumor targeting gene vaccination, fungal infection ,skincare and topical product

DEFINITION
Liposomes are concentric of bilayered vesicles in which an aqueous volume is entirely enclosed by a membranous lipid bilayer composed of natural or synthetic phospholipid. e.g. Doxil , daunoxome ,amphotericin -B

What is a liposome?
y Spherical vesicles with a phospholipid bilayer

Hydrophilic

Hydrophobic

PHOSPHOLIPIDS
Polar Head Groups

Three carbon glycerol

CLASSIFICATION
Basing upon bilayered formed and diameter of resultant vescicle ` SUV (Single bilayer) ` LUV (Single bilayer) ` MLV(Several bilayer) ` OLV Basing on method of liposome preparation ` Reverse phase vesicle ` French press vescicle ` Ether injection vescicle ` Extrusion technique Basing on composition and application y Long circular liposome y Immuno liposome y pH sensitive liposome y Conventional liposome y Fusojenic liposome

COMPOSITION
Phospholipid e.g. lecithin, dipalmitoyl PT serine y Cholesterol y Antioxidant e.g. BHT, alpha-tocopherol y Charge inducing substance e.g. diacyl glycerol , steryl amine y Agent that increse the liposomal circulation e.g. sphingomyelin
y

In preparation of liposome most commonly used materials are:Phospholipids. Sphingolipid. Glyco-sphingolipid. Sterols. Metabolic fate of bi-layer forming lipid. Synthetic phospholipids. Polymeric materials. Polymer bearing lipid. Cationic lipid. Other substances

y METHODS OF LIPOSOME

PREPARATIONS

Passive loading technique

Active loading technique

Mechanical dispersion method

Solvent dispersion method

Detergent removal method

Lipid film hydration Micro emulsification Sonication Membrane extrusion

ethanol injection Ether injection

column chromatography Dialysis Adsorption

PREPARATION OF LIPOSOMES
Handling of liposomes
y Generally

liposomes composed of lecithin:cholesteral: phosphtidyl glycerol in 0.9 : 1.0 : 0.1. These lipids are oxidized if not handled properly. y So it is stored as solids or in organic solvent at -20 0C or at -70 0C.and in ground glass stopper or polypropylene container in dark place and N2 is added to remove O2 to prevent oxidation.

cholesterol

Lecithin

charge

Dispersion in organic solvent

Solution in organic solvent Drying Thin film

Dispersion (hydration)

Procedure
Four basic steps include Drying down lipid from organic solvent. Dispersion of lipids in aqueous media. Purification of resultant liposomes. Analysis of the final product.

Liposome suspension

Preparation of MLVs by hand shaking or rotary flash evapourator

Hand shaking vaccum Rotary flash evapourator Film formation N2 Dried films

hydration

Storage under N2
At 4 0c

Liposomal dispersion

Film stacks dispersed in aq. phase

Micro emulsification liposome

Separation into two streams Collision at right angle Vesicles of required dimension

Filter 5micrometer

Reservoir of MLVs

air

SONICATION METHOD MLVs

ultrasonification Small vescicle

EXTRUSION METHOD
Big size liposome Dispersion medium Poly carbonate filter Extrude liposome

SOLVENT DISPERSION METHOD

Ether injection Lipid + ethanol solution slow injection Aqueous phase SUVs

Ethanol injection Lipid + ethanol solution Rapid injection Aqueous phase SUVs

CHARACTERISATION
CHEMICAL ` Affinity for various tissue : Modified by synthesizing liposomes containing phospholipids with various fatty acid chain configurations Solid or liquid at defined temperatures Altering the charge on the liposome vesicles influences its distribution in the body. x Negatively charged vesicles enter the cell by fusion. x Neutral vesicles are incorporated into the cell by phagocytosis.

PHYSICAL

y Microparticles ranging in size from 0.03 to 10

micrometer y Bilayer of phospholipid encapsulating an aqueous space . y Amphipathic lipid molecules can be used to form the bilayer.

STABILITY TESTING
CONDITION FOR TESTING 1. ONE MONTH AT 45 . 2. ONE MONTH AT 4 . 3. SIX MONTHS AT 37 . 4. 12-24 MONTHS AT ROOM TEMP. 5. 12-24 MONTHS AT VARIOUS LIGHT INTENSITIES. 6. 2-3 FREEZE THAW CYCLES(-20 to 25 ). 7. 6-8 TIMES HEAT- COOL CYCLES(5 to 45 ). 8. 24-48 HOURS ON A RECIPROCATING STAKER AT 60 CYCLE/MINUTES.

APPLICATION
y Liposomes as drug /protein delivery vehicle. y Liposomes in antineoplastic agents, antimicrobial compounds, y y y y y

immunomodulators. Increase in the efficacy and reduced toxicity. Facilitated transfer to fungal cells. Liposomes in cosmetic and dermatology. Liposomes in enzyme immobilization and bioreactor technology. Liposomes as radiopharmaceutical and radiodiagonistic carrier.

Phospholipid:AmB ratio AmB

Cholesterol - only few %moles Lipid

Exact Mechanism of liposomes not understood Decrease in toxicity

No decrease in effectiveness of drug against fungi

Liposomal Formulation of AmB

CONCLUSION
y Liposomes have been realized as extremely useful carrier

system, and tools in various scientific domain . The flexibility in their behaviour ,can be used for the drug delivery through any route of administration and for any drug material irrespective of their physiological property .

y The safety and efficacy of current treatments

may be improved if their delivery rate, biodegradation and site specific targeting can be predicted, monitored and controlled.

REFERENCE
y Targeted and controlled drug delivery novel carrier system y y y y y

by S.P. Vyas and R.K. Khar NDDS by Y.W. Chein , marcel dekker NDDS by Joseph RR Robinson and vincent ILL.Lee Advances in liposomal therapeutics by sanjay K. jain. Encyclopedia of pharmaceutical technology, 3rd edition. Pharmaceutical dosage form-dispersed system.

THANK YOU

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