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
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Brian Tracy
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