Liposomes by Mr. Vishal Shelke https://youtube.com/vishalshelke99 https://instagram.com/vishal_stagram Liposomes Sub :- Novel Drug Delievery Systems, Sterile Products Formulation & Technology M.Pharm Sem II Savitribai Phule Pune University Introduction :- Liposomes are vesicular structures composed of a lipid bilayer. These vesicular structures can be used as a vehicle for administration of nutrients and drugs. Liposomes are concentric bilayered vesicles in which an aqueous volume is entirely enclosed by a membranous lipid bilayer. Liposomes consist of Cholesterol, Phospholipid and drug molecule Classification of Liposomes :- Small Unilamellar (SUV) [20-100nm] Medium Unilamellar (MUV) Large Unilamellar (LUV) [>100nm] Giant Unilamellar (GUV) [>1μm] Multi Lamellar Vesicles (MLV) [0.5nm] Oligolamellar Vesicles (OLV) Multi Vesicular (MV) [>1μm] ADVANTAGES  Provides selective passive targeting to tumor tissues. Increased efficacy and therapeutic index. Increased stability via encapsulation. Reduction in toxicity of the encapsulated agents. Improved pharmacokinetic effects (reduced elimination, increased circulation life times). DISADVANTAGES low solubility short half life high production  cost less stability leakage and fusion of encapsulated drug sometimes the phospholipid layer undergoes oxidation and hydrolysis reaction Methods of Preparation of Liposomes 1 Mechanical Dispersion Method Lipid film hydration by hand shaken MLVs Micro emulsification Sonication French pressure cell Dried reconstituted vesicles Membrane Extrusion Method 2 Solvent Dispersion Method Ethanol injection Ether injection Double emulsion vesicles Reverse phase evaporation vesicles 3 Detergent Removal Method

2.  Introduction
 Classification of Liposomes
 Advantages & Disadvantages
 Methods of Preparation
 Vesicular ocular drug delivery system – liposomes
 Evaluation of Liposomes
 Applications
 References

3. Introduction :-
Liposomes are vesicular structures composed of a lipid bilayer.
These vesicular structures can be used as a vehicle for administration
of nutrients and drugs.
 Liposomes are concentric bilayered vesicles in which an aqueous
volume is entirely enclosed by a membranous lipid bilayer.
 Liposomes consist of Cholesterol, Phospholipid and drug molecule

4. Classification of Liposomes :-
•Small Unilamellar (SUV) [20-100nm]
•Medium Unilamellar (MUV)
•Large Unilamellar (LUV) [>100nm]
•Giant Unilamellar (GUV) [>1μm]
•Multi Lamellar Vesicles (MLV) [0.5nm]
•Oligolamellar Vesicles (OLV)
•Multi Vesicular (MV) [>1μm]

5. ADVANTAGES
•Provides selective passive targeting to tumor tissues.
•Increased efficacy and therapeutic index.
•Increased stability via encapsulation.
•Reduction in toxicity of the encapsulated agents.
•Improved pharmacokinetic effects (reduced elimination,
increased circulation life times).

6. DISADVANTAGES
•low solubility
•short half life
•high production cost
•less stability
•leakage and fusion of encapsulated drug
•sometimes the phospholipid layer undergoes oxidation and
hydrolysis reaction

7. Methods of Preparation of Liposomes
Mechanical Dispersion
Method
Solvent Dispersion
Method
Lipid film hydration by
hand shaken MLVs
Micro emulsification
Sonication
French pressure cell
Dried reconstituted
vesicles
Membrane Extrusion
Method
Ethanol injection
Ether injection
Double emulsion
vesicles
Reverse phase
evaporation vesicles
Detergent Removal
Method

8. Lipid film hydration by Hand Shaken MLVs
Lipid Mixture in Chloroform: Methanol (2:1v/v) in 250 ml flask
Rotate the flask on rotary evaporator for 60 rpm at 300
C for 15 mins.
Lyophilizer to remove residual solvents
Hydration of lipid in saline phosphate buffer for 30 mins
Allow to stand for 2 hrs. at RT for swelling to give MLVs.

9. Microemulsification
Microfluidizer

10. Sonication

11. French Pressure Cell Method
This method involves the extrusion of MLV at 20,000 psi at 4°C
through a small orifice. The method has several advantages over
sonication method. The method is simple, rapid, reproducible and
involves gentle handling of unstable materials. The resulting liposomes
are somewhat larger than sonicated SUVs.
Dried Reconstituted Vesicles (DRVs)
In this method, water soluble materials to be entrapped, are added to
the suspension of empty SUV’s & they are dried together, so the
material for inclusion is present in the dried precursor lipid before the
final step of addition of aqueous medium.

12. Membrane Extrusion Method
 Liposomes passed through membrane of defined pore size.
 LUVs as well as MLVs can be processed.
 Vesicle contents are exchanged with dispersion medium during
breaking and resealing of phospholipid bilayers as they pass through
the polycarbonate membrane.
 For high entrapment, the water soluble compounds should be
present in suspending medium during the extrusion process.

13. Solvent Dispersion Methods
Ethanol Injection Method

14. Ether Injection Method

15. Double Emulsification Method
In this process, an active ingredient is first dissolved in
an aqueous phase which is then emulsified in an organic
solvent of a polymer to make a primary w/o emulsion.
 This primary emulsion is further mixed in an emulsifier-
containing aqueous solution (w2) to make a w/o/w double
emulsion.
 The removal of the solvent leaves microspheres in the
aqueous continuous phase, making it possible to collect
them by filtering or centrifuging.

16. Reverse Phase Evaporation Method
 Lipid, organic solvent and aqueous solution are i. mixed,
ii. sonicated, iii. formation of w/o emulsion.
 Then evaporated to remove the organic solvent.
 Lipids form a phospholipid bilayer on vigorous shaking ,
water droplets collapse and formation of LUV’s takes place.

17. Detergent Removal Method
The detergents (cholate, triton X-100, octylglucoside) at their critical
micelles concentrations have been used to solubilize lipids. As the
detergent is removed the micelles become progressively richer in
phospholipid and finally combine to form LUVs.
The detergents are removed by dialysis .
A commercial device called LIPOPREP which is a dialysis system is
available for the removal of detergents.
Other techniques have been used for the removal of detergents are Gel
Chromatography involving a column of Sephadex G-25.

18. VESICULAR OCULAR DRUG DELIEVERY SYSTEM –
LIPOSOMES
Deliver the drug at a predetermined rate and should release the
drug at the specific site of action in therapeutically active
concentration.
Drug delivery via vesicles provides prolonged as well as controlled
drug delivery at the targeted corneal surface.
They are having an intimate contact with the corneal and
conjunctival surfaces.
Which is desirable for drugs that are poorly absorbed, the drugs
with low partition coefficient, poor solubility or those with medium
to high molecular weights.

19. 1. Visual Appearance
2. % Drug Encapsulated
3. Phase Behaviour
4. Drug Release Rate
5. Determination of Lamillarity
6. Particle Size

20.  Cancer chemotherapy –
Liposomes are successfully used to entrap anticancer drugs. This
increases circulation life time, protects from metabolic degradation.
 Liposomes as carrier of drug in oral treatment –
• Steroids used for arthritis can be incorporated into large MLVs.
• Alteration in blood glucose levels in diabetic animals was obtained
by oral administration of liposome encapsulated insulin.
 Liposomes for pulmonary delivery –
Inhalational devices like nebulizers are use to produce an aerosol of
droplets containing liposomes.

21.  Liposomes can enhance the permeation of poorly
absorbed drug molecules by binding to the corneal surface
and improving residence time E.g. Ciprofloxacin
 Liposomes can improve pharmacokinetic profile,
enhance therapeutic effect, and reduce toxicity associated
with higher dose E.g. fluconazole
 Liposomes have been widely investigated for the
treatment of both anterior and posterior segment eye
disorders.

22. 1. Controlled And Novel Drug Delivery’, “Jain N.K.’’, CBS
Publisher And Distributors. Page No. 304-352.
2. Targeted And Controlled Drug Delivery, Novel Carrier Systems
“Vyas S.P. And Khar R.K.’’, CBS Publishers Page No.181 -195
3. Liposome- As Drug Carriers-international Journal Of Pharmacy &
Life Sciences - Himanshu Anwekar, Sitasharan Patel And A.K
Singhai.
4. https://slideshare.net
5. https://pharmatutor.org

23. Also available on Youtube!
Youtube :- https://youtube.com/vishalshelke99
Instagram :- https://instagram.com/vishal_stagram

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