This document discusses liposomes, which are spherical vesicles made of lipid bilayers that can encapsulate drugs for targeted drug delivery. Liposomes have a microscopic spherical structure and are made of one or more concentric lipid bilayers composed of natural or synthetic phospholipids. They can encapsulate both hydrophilic and hydrophobic drugs within their aqueous interior or lipid bilayer. The main components of liposomes are phospholipids and cholesterol. Phosphatidylcholine is a commonly used phospholipid that has a hydrophilic head and hydrophobic tails. Cholesterol is also incorporated and affects the fluidity and permeability of the membrane. Liposomes are classified based on structure, method of preparation, composition, and provide advantages like targeted drug delivery and

2. INTRODUCTION:-
• Special form of Drug delivery system.
• API/Drug delivered at the site of action.
• Bi-layered vesicles.
• Size range from 50 to several micro-meters in diameter in diameter.
• Microscopic sphere structure.
• Made up of one or more concentric lipid bi-layer.
• These lipid bilayer composed of natural or synthetic phospholipids.
• Aqueous volume entirely enclosed by a membranous lipid bilayer.
• Able to carry both Hydrophilic and Hydrophobic Drug.
• Liposome main component is :- PHOSPHOLIPIDS AND CHOLESTROL.

5. STRUCTURAL COMPONENTS OF LIPOSOMES
• The main components of liposome are:-
1. Phospholipids
2. Cholesterol

6. Phospholipids:-
• Structural component of biological membrane.
• Most common phospholipids used in liposomal preparation is
Phosphatidylcholine(PC).
• Phosphatidylcholine is an amphipatic molecule containing:-
A hydrophilic polar head group ,Phosphocholine.
A glycerol bridge.
A pair of hydrophobic acyl hydrocarbon chain.
Phosphatidylcholine are not soluble in water.
In aqueous media - aling themselves closely in planar bilayer sheets,
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Minimize the unfavourable action
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Between bulk aqueous phase and long hydrocarbon fatty chain
Sevral phospholipids that used in pptn. If liposomes such as:-
Dilaurylphosphotidylcholine(DLPC):,Dipalmitoyl phosphotidyl choline(DPPC) ETC.

7. cholesterol
• The role cholesterol in formulation of liposome was given below:-
In liposomes bilayer produce major changes in pptn. Of the membrane.
Cholesterol itself doesn’t form a bilayer structure.
Cholesterol act as a buffer nature.
Due to fluidity buffer nature make membrane less ordered & slightly more
permeable.
It can be incorporated into phospholipid membrane in very high concentration up
to 1:1 on even 2:1 molar ratios of cholesterol to phospholipids.

8. ADVANTAGE OF LIPOSOME:-
Provide selective passive targeting to tumour tissue.
Increase efficacy &therapeutic index.
Increased stability via encapsulation.
Reduced toxicity of encapsulation agent.
Site avoidance effect.
Improved pharmacokinetic effect.
Flexibility to couple with site specific ligand to achieve active targeting.

9. DISADVANTAGE OF LIPOSOMES:-
Production cost is high.
Leakage &fusion of encapsulated.
Sometimes phospholipids undergo oxidation& hydrolysis like reaction.
Short half life low solubility.
CLASSIFICATION OF LIPOSOMES:-
STRUCTURE.
METHOD OF PREPARATION.
COMPOSITION.
CONVENTIONAL LIPOSOMES.
SPECIALITY LIPOSOMES.

10. CLASSIFICATION BASED ON THE STRUCTURE:-
Vesicle type abbreviation diameter size no of lipid-layer
Unilamellar UV All size range ONE
Small unilamellar SUV 20-100nm ONE
Medium unilamellar MUV More than 100nm ONE
Large unilamellar LUV More then 10nm ONE
Giant unilamellar GUV More then 0.1um ONE
Oligo lamellar OLV 0.1-1.0um Approx.0.5
Multi lamellar MLV More than 0.5um 5-25
Multi vesicular MV More than 1.0um Multi-compartment-
structure

11. BASED ON METHOD OF PREPRATION:-
PREPRATION METHOD VESICLE TYPE
Single or oligolamellar vesicle made by reverse- REV
phase evaporation
Multi-lamellar vesicle made by reverse phase- MLV-REV
evaporation method
 stable pluri lamellar vesicle SPLV
Frozen and thawed multilamellar vesicle FAT-MLV
Vesicle prepared by extrusion technique VET
Dehydration- rehydration method DRV

12. CLASSIFICATION BASED ON COMPOSITION:-
TYPES ABBREVATION COMPOSITION
Conventional CL --Neutral or negativity charged
phospholipids and cholesterol.
Fusogenic RSVE --Reconstituted sendai virus
envelope.
PH-sensitive ------ --Phospholipids such as PER or
DOPE with either CHEMS or OA.
Cationic ------ --Cationic lipid with DOPE
Long circulation LCL --Neutral , high temp. ,cholesterol
And 5-10% PEG,DSP.
Immuno. IL --CL on LCL with attached-
monoclonal antibody or-
Recognitions sequences.

13. CLASSIFICATION BASED UPON CONVENTIONAL LIPOSOMES:-
Natural lecithin mixture.
Synthetic identical , chain phospholipids.
Liposomes with glycolipids.

14. Structure of liposomes

15. METHOD OF PREPARATION:-
A). PASSIVE LOADING TECHNIQUE:-
1). Mechanical Dispersion
Lipid hydration method.
Micro emulsification.
Sonication.
French pressure cell method.
Membrane extrusion.
Dried reconstituted vesicles.
Freeze-thaw method.

16. 2).SOLVENT DISPERSION:-
Ethanol injection method.
Ether infusion method.
Double emulsification.
Reverse-phase evaporation.
3).DETERGENT REMOVAL
B).ACTIVE LOADING TECHNIQUE:-
Proliposome
Lyophilization

17. A). PASSIVE LOADING TECHNIQUE:-
1.MECHANICAL DISPERSION
a). Lipid hydration method:-
• Common &widely used method for preparation of MLV.
• Round bottom flask used for preparation.
Method
- Formation of thin film.
- By drying the lipid solution.
- Then hydrating the film by adding aqueous buffer and vertexing the dispersion.
- Depending on the solubility the compound to be capsulated are added either to
aqueous buffer or to organic solvent containing lipids.
- Finally , MLV formed by removing organic layer bypassing Nitrogen.

18. DISADVANTAGE:-
- Low internalvolume.
- Less encapsulation efficiency.
- Varying size.

19. b). MICRO-EMULSIFICATION:-
Method used for preparing small lipid vesicles in commercial quantities.
Using high shearing stress generated from high pressure homogenizers.
Adjusting speed rotation from 20-200.

20. c).Sonication:-

21. DRAW-BACK:-
Very low internal volume/encapsulation efficiency , degradation of phospholipids ,
exclusion of large molecule , metal contamination.

22. d). French pressure cell method:-
• Extrusion of MLV through a small orifice at 20,000 psi at 4°c.
• Advantage:- method is simple, reproducible and involve gentle handling of unstable
material.
• Disadvantage:- difficult in achiving temp. & less working volume.(about 50ml.
Max.).

23. e). Membrane extrusion:-
Suspension of heterogeneous size liposomes,
Passed through a polymer filter,
Having web like construction providing-
Capillary pore , network of inter-connected & a membrane thickness of at least
about 100 microns.
The processed liposome having narrow size distribution & selective avg. size less
than about 0.4 micron.

24. f).Dried reconstituted vesicles:-
Liposomes are added to aqueous solution
↓
Containing drugs or mixed with a lyophilized protein.
g).freeze-thaw-method:-
in this method SUVs are rapidly frozen.
The fusion of SUVs during the processing of freezing & thawing leads to the
formation of ULV.
This type of fusion strongly inhibit by increasing the ionic strength of the medium &
by increasing the phospholipids concentration.
Entrapment efficiencies 20 to 30%

25. 2).SOLVENT DISPERSION
a).ethanol injection method:-
 a lipid solution of ethanol is rapidly injected to an excess of buffer,
leads to the immediate
formation of MLVs.
DRAW BACK
Particles may be with heterogenous size distribution (30-110nm).
Removal of ethanol is difficult.

26. b).ether infusion method:-
A solution of lipids dissolved in ether or ether methanol mixture
↓
slowly inject to an aqueous solution of drug
↓
formed encapsulated at temperature 55 °c - 65 °c.under reduced pressure.
↓
Remove ether under vaccum - reformed of liposomes.
Draw-back
Exposure of drugs & lipids to organic solvent and high temperature,that’s cause
dehydration.
Size vary-> 70-190nm.

28. c).double emulsification:-
A primary emulsion is prepared by dissolving aqueous phase(w1),
↓
Emulsified in an organic solvent of a polymer
↓
To make a primary W1/O(1 °W1/O) emulsion.
↓
Then 1 ° emulsion mixed further in emulsifier- that containing aqueous
solution(W2)
↓
To make W1/O/W2 double emulsion.

29. d).reverse-phase evaporation:-
In this method , lipid mixture is taken in round bottom flask
↓
removed solvent under reduced pressure by a rotary evaporation.
↓
system purged with nitrogen and the lipid are re-dissolved in organic phase
↓
reverse phase vesicle will be formed
 Usually solvent used are Diethyl ether &isopropyl ether.
Aqueous-phase contain drug to encapsulated ,
↓
when added after the lipid are re-dispersed in this phase.
↓
system kept under continuous nitrogen & the two phase system is sonicated until the mixture becomes clear one-phase
dispersion.
↓
The mixture placed on the rotary evaporator and the removal of organic solvent is done until a gel is formed followed by
removal of non-encapsulated material.
↓
The resulting liposomes are called reverse-phase evaporation vesicles.

31. 3).DETERGENT REMOVAL:-
lipid are solubilized by the detergent at their critical micellar concentration.
The micelles become progressively riches in phospholipid as the detergent is
removed by dialysis and finally combine to formed LUVs.
Advantage :- outstanding reproducibility &production of liposome population of
homogenous size.
Drawback:-retention of detergent contaminants.

33. B). ACTIVE LOADING TECHNIQUE:-
a).proliposome:-
Lipids and drugs are coated onto soluble carriers to form free-flowing granular
material in proliposomes---
which form isotonic liposomal suspension on hydration.
ADVANTAGE:- provide opportunity for cost-effective,
large-scale manufacture of liposomes-containing particularly lipophilic
drugs.

34. b).lyophilization:-
• Removal of water from product in the frozen state at extremely reduced pressure
is called lyophilization (freezing drying).
• The process is generally used to dry product that are thermolabile which may be
destroyed by heat-drying.
• This technique has a great potential to solve long term stability problem with
respect to liposomal stability.
• Leakage of entrapped material may take place during the process of freeze-drying
and on reconstitution.

35. CHARACTERIZATION OF LIPOSOMES:-
• The behaviour of liposomes in both physical & biological system is governed by the factor such as-
PHYSICAL SIZE, MEMBRANE PERMEABILITY,PERCENT ENTRAPPED SOLUTES,CHEMICAL
COMPOSITION AS WELL AS QUALITY AND PURITY BOF THE STARTING MATERIAL.
• PHYSICAL-PROPERTIES:- CHEMICAL-PROPERTIES:-
a)Size and it’s distribution. a) quantitative determination of phospholipids.
1).microscopic method. b) phospholipids hydrolysis.
2).laser light scattering. c ) phospholipids oxidation.
3).Gel permeation. d) cholesterol analysis.
b) Surface charge.
c) percent-capture.
d) Entrapped volume.
e) lamellarity.
f) Face behaviour of liposome.
g) Drug release.

36. APPLICATION:-
• Used in cancer chemo-therapy & neoplasia.
• Used as a carrier for vaccines.
• Used as immunological adjuvants.
• Used as carrier of antigens.
• Used as carrier of drugs in oral treatment.
• Used for topical drug delivery.
• Used for pulmonary delivery of drugs
• Used as storage of disease…..etc.

37. • THANK YOU