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Liposomal drug delivery system
1. P R E S E N T E D B Y
Z A H I D H U S A I N
M . P H A R M
( P H A R M A C E U T I C S )
FA C U LT Y O F P H A R M A C Y, I U , L U C K N O W
U N D E R G U I D A N C E O F D R . S . P S I N G H
LIPOSOMAL DRUG
DELIVERY SYSTEM
2. INTRODUCTION
Liposomes are concentric bilayered vesicles in which
an aqueous core is entirely enclosed by a
membranous lipid bilayer mainly composed of
natural or synthetic phospholipids.
The size of a liposome ranges from 20 nm up to
several micrometers.
The lipid molecules are usually phospholipids-
amphipathic moieties with a hydrophilic head group
and two hydrophobic tails.
5. ADVANTAGES OF LDDS
Suitable for delivery of hydrophobic, hydrophilic and amphipatic drugs and
agents
Chemically and physically well characterized entities
Biocompatible
Use as carrier for suitable for controlled release drug delivery.
Suitable to give localized action in particular tissues.
Suitable to administer via various routes
Increased efficacy and therapeutic index.
Reduction on toxicity of the encapsulation agent.
Improved pharmacokinetic properties.
Can be made into Varity of drug.
Minimum antigenicity.
6. Disadvantage of LDDS
Their rapid clearance from circulation due to uptake,
by the reticuloendothelial system(RES), primarily in the
liver
Leakage of encapsulation drug delivery during storage.
Batch to batch variation.
Once administered, can’t removed.
Difficult in large scale manufacture and sterilization.
Physical /chemical stability
Very high production cost
Possibility of dumping due to faulty administration.
7. CLASSIFICATION OF LIPOSOME'S
1) Based on structural parameters:
MLV : Multilamellar large vesicles- >0.5 μm
GUV : Giant unilamellar vesicles->1 μm
LUV : Large unilamellar vesicles->100nm
MUV : Medium sized unilamellar vesicles
SUV : Small unilamellar vesicles-20-100nm
UV : Unilamellar vesicles (all in size)
OLV : Oligolamellar vesicles- 0.1-1 μm
MV : Multivesicular vesicles->1 μm
8. Cont…
2) Based on method of liposome preparation:
REV : Single or oligolamellar vesicles made by reverse-
phase evaporation method
MLV-REV : Multilamellar vesicles made by reverse
phase evaporation method
SPLV : Stable plurilamellar vesicles
FATMLV : Frozen and thawed MLV
VET : Vesicles prepared by extrusion technique
DRV : Dehydration-rehydration method
9. Cont…
3) Based on the composition and application:
Conventional liposome : Neutral or negatively charged
Phospholipid
Fusogenic liposome : Reconstitute sendai virus envelop
Cationic liposome : Cationic lipid
Long circulatory liposome : Neutral high Transition
temperature liposome
pH sensitive liposome : Phospholipid like Phosphatidyl
ethanolamine
Immuno liposome : Long circulatory liposome with
attached monoclonal antibody
10.
11. METHODS OF LIPOSOME
PREPARATION
PASSIVE LOADING:
Involves loading of the entrapped agents before or
during the manufacturing procedure
ACTIVE OR REMOTE LOADING:
Certain types of compounds with ionizable groups and
those with both lipid and water solubility , can be
introduced into the liposomes after the formation of the
intact vesicles
12. 1. Passive loading technique
A) Mechanical dispersion method:
Lipid hydration by hand shaking or freeze drying
Micro emulsification
Sonication
French pressure cell
Membrane extrusions
Dried reconstituted vesicle
Freeze thawed liposome
20. ETHANOL/ETHER INJECTION
ETHANOL INJECTION:
An ethanol solution of lipids is injected rapidly through a fine
needle into an excess of saline or other aq. medium
This method has low risk of degradation of sensitive lipids
The vesicles of 100 nm size may be obtained by varying the conc.
Of lipid in ethanol or by changing the rate of injection of ethanol
solution in preheated aqu. solution.
ETHER INJECTION:
Involves mixing of organic phase into aqu. Phase at the temp. of
vaporizing the organic solvent
It has low encapsulation efficiency
22. 2. ACTIVE LOADING TECHNIQUE
1. PROLIPOSOME:
Lipid and drug are coated onto a soluble carrier to form free-flowing granular
material in pro-liposome which forms an isotonic liposomal suspension on
hydration. The pro-liposome approach may provide an opportunity for
containing particularly lipophilic drugs.
2. LYOPHILIZATION:
The removal of water from products in the frozen state at extremely reduced
pressure is called lyophilization (freeze drying). The process is generally used
to dry products that are thermolabile which may be destroyed by heat-drying.
This technique has a great potential to solve long term stability problems with
respect to liposomal stability. Leakage of entrapped materials may take place
during the process of freeze- drying and on reconstitution.
23. Why Use Liposomes in Drug Delivery?
Drug Targeting at specific
-Cell
-Tissue
-Receptor
-pH range
Inactive: Unmodified liposomes gather in specific tissue
reticuloendothelial system
Active: alter liposome surface with ligand (antibodies,
enzymes, protein A, sugars)
Protection: Decrease harmful side effects (Change where
drug accumulates in the body)
24. Cont…
Pharmacokinetics
- Efficacy and toxicity
-Changes the absorbance and biodistribution
- Deliver drug in desired form
- Deliver drug in desired form
Protection
- Decrease harmful side effects (Change where drug accumulates in the
body)
Release
- Affect the time in which the drug is released
- Prolong time
- Increase duration of action and decrease administration
Dependent on drug and liposome properties Liposome composition, pH and
osmotic gradient, and environment.
25. CHARACTERIZATION OF LIPOSOMES
1. Physical Characterization:
Vesicle shape and surface Morphology:
Transmission electron microscopy, freeze-fracture electron microscopy.
Surface charge: Free-flow electrophoresis.
Lamellarity:
Small angle X-ray scattering, freeze-fracture electron microscopy, 31P-NMR.
Phase behaviour:
Freeze-fracture electron microscopy, differential scanning calorimetry.
Percent capture/percent of free drug:
Minicolumn centrifugation, gel exclusion, ion-exchange chromatography,
radiolabelling.
26. Cont…
2. Chemical Characterization:
Phospholipid concentration:
Lipid phosphorous content using Barlett assay, HPLC
Cholesterol concentration:
Cholesterol oxidase assay and HPLC
Drug concentration:
Appropriate method given in monograph
Phospholipid peroxidation:
UV absorbance, TBA , indometric and GLC
Phospholipid hydrolysis: HPLC and TLC
Cholesterol auto-oxidation: HPLC and TLC
27. Cont…
pH: pH meter
Osmolarity: Osmometer
Anti-oxidant degradation: HPLC and TLC
3. Biological Characterization:
Sterility:
Aerobic or anaerobic cultures
Pyrogenicity:
Limulus amebocyte lysate (LAL) test
Animal toxicity:
Monitoring survival rates, histology and pathology
28. APPLICATION OF LIPOSOMES
Liposomes as drug/protein delivery vehicles.
Enhanced drug solubilization.
Enzyme replacement therapy and lysosomal storage
disorders.
Liposomes used in antimicrobial, antifungal and
antiviral therapy.
Increase bioavailability.
Liposomes used in tumour therapy.
Vehicle for macromolecules as cytokines genes.
29. Cont…
Carrier of small cytotoxic molecules.
Genetic vaccination
Liposomes as artificial blood surrogates
Liposomes as radiopharmaceutical and radio diagnostic
carriers
Liposomes used in cosmetics and dermatology
Liposomes used in enzyme immobilization and
bioreactor technology.
Liposomes in gene delivery
30. REFERENCE
S.P.VYAS, R.K.KHAR “Targeted and Controlled Drug
Delivery Novel Carrier Systems, first edition 2002, CBS
publisher and distributer pvt. Ltd Pg.no;172-212
Encyclopaedia of controlled released drug delivery
system, volume 2.
http//www.liposome.com
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