liposomes final

8/4/2019 Liposomes Final

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CONTENT


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Introductiony 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 bi-

layered 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 systemHowever 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


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DEFINITION

Liposomes are concentric of bilayered

vesicles in which an aqueous volume is

entirely enclosed by a membranous lipid

bilayer composed of natural or syntheticphospholipid.

e.g. Doxil , daunoxome ,amphotericin -B


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What is a liposome?What is a liposome?

ySpherical vesicles with a phospholipid bilayer

Hydrophilic

Hydrophobic


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PHOSPHOLIPIDS

Polar Head Groups

Three carbon glycerol


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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 liposomey Immuno liposome

y pH sensitive liposome

y Conventional liposome

y

Fusojenic liposome


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COMPOSITIONy Phospholipid

e.g. lecithin, dipalmitoyl PT serine

y Cholesteroly 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. sphingomyelinIn 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


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y METHODS OF LIPOSOMEPREPARATIONS

Passive loading technique Active loading technique

Mechanical dispersion

methodSolvent dispersion method Detergent removal

method

Lipid film hydration

Micro emulsification

Sonication

Membrane extrusion

ethanol injection

Ether injection

column

chromatography

Dialysis

Adsorption


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PREPARATIONOFLIPOSOMES

Handling of liposomesy Generally liposomes composed of

lecithin:cholesteral: phosphtidylglycerol in 0.9 : 1.0 : 0.1. These lipidsare oxidized if not handled properly.

y So it is stored as solids or in organicsolvent at -20 0C or at -70 0C.and inground glass stopper or polypropylenecontainer in dark place and N2 isadded to remove O2 to preventoxidation.

ProcedureFour basic steps include

Drying down lipid from organicsolvent.Dispersion of lipids in aqueousmedia.Purification of resultant liposomes.Analysis of the final product.

cholesterol Lecithin charge

Dispersion in organic solvent

Solution in organic solvent

Drying

Thin film

Liposome suspension

Dispersion (hydration)


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Hand shakingvaccum

Film formation

Dried films

hydration

Storage under N2At 4 0c

Liposomal

dispersion

Film stacks dispersed in

aq. phase

Rotary flash

evapouratorN22

Preparation of MLVs by hand shaking or rotary flash

evapourator


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Micro emulsification liposome

Separation into

two streams

Collision at right angle

Vesicles of

required

dimension

Reservoir ofMLVs

air

Filter5micrometer


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SONICATIONMETHOD

EXTRUSIONMETHOD

MLVs

ultrasonificationSmall vescicle

Big size liposome

Dispersion medium

Poly carbonate filter

Extrude liposome

SOLVENT DISPERSION

METHOD

Ethanol injection

Lipid + ethanol solution

Aqueous phase

SUVs

Ether injection

Rapid injection

Lipid + ethanol

solution

slow injection

Aqueous phase

SUVs


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CHARACTERISATION

CHEMICAL

`

Affinity for various tissue : Modified by synthesizing liposomescontaining 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.


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PHYSICAL

yMicroparticles ranging in size from 0.03 to 10

micrometer

yBilayer of phospholipid encapsulating an aqueous

space .

yAmphipathic lipid molecules can be used to form

the bilayer.


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STABILITYTESTINGCONDITION FORTESTING

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.


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APPLICATION

y Liposomes as drug /protein delivery vehicle.

y Liposomes in antineoplastic agents, antimicrobial compounds,

immunomodulators.

y

Increase in the efficacy and reduced toxicity.y Facilitated transfer to fungal cells.

y Liposomes in cosmetic and dermatology.

y Liposomes in enzyme immobilization and bioreactor technology.

y Liposomes as radiopharmaceutical and radiodiagonistic carrier.


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AmB

Lipid

Liposo

mal For

mulation of

AmB

Phospholipid:AmB ratio

Cholesterol - only

few %moles

Exact Mechanism of liposomes not understood

Decrease in toxicity

No decrease in effectiveness of drug against fungi


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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 .


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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.


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REFERENCE

y Targeted and controlled drug delivery novel carrier system

by S.P. Vyas and R.K. Khar

y NDDS by Y.W. Chein , marcel dekker

y

NDDS by JosephRR

R

obinson and vincent ILL.Leey Advances in liposomal therapeutics by sanjay K. jain.

y Encyclopedia of pharmaceutical technology, 3rd edition.

y Pharmaceutical dosage form-dispersed system.


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THANK YOU

Confidence is a habit that can be developed byacting as if you already had the confidence you

desire to have

Brian Tracy

liposomes final

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