liposome...

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.

3. Cont…

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

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

13. Cont…
B) Solvent dispersion method:
 Ethanol injection
 Ether injection
 Double emulsion vesicle
 Reverse phase evaporation vesicle
 Stable pluri lamellar vesicle
C) Detergent removal method:
 Detergent (cholate, alkyl glycoside, Triton x-100) removed from mixed
micelles
 Dialysis
 Column chromatography
 Dilution
 Reconstituted sendai virus enveloped vesicle

14. 1. PASSIVE LOADING TECHNIQUE
A. MECHANICAL DISPERSION METHOD

15. 1. Hand Shaken MLV

16. Cont…

17. 2. Non Shaken vesioles

18. 3. Pro Liposome

19. 4. Freeze Drying

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

21. Cont…

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
 Slideshare
 Wikipedia

31. THANK
YOU