INTRODUCTION:

Paul Ehrlich in 1906 initiated the era of development for targeted delivery when he discovered a drug delivery mechanism that would target drug directly to diseased cells that called magic bullets. Liposomes are small artificial vesicles of spherical shape that can created from cholesterol and natural non-toxic phospholipid, liposomes were first described by British hematologist Alec D Bangham in 1961 at the Babraham Institute in Cambridge they were discovered when Bangham and R.W Horne were testing the institute new electron microscope by adding negative strain to dry phospholipid. Bangham had called his lipid structure multimellar smectic mesosomes or sometimes ‘Banghasomes’¹

Fig. Structure of Liposome

Advantages of Liposomes:

· Provide selective passive targeting to tumor tissues.

· Increased efficiency and therapeutic index.

· Increased stability via encapsulation.

· Reduction in toxicity of encapsulated agent.

· Improved pharmacokinetics effects.

· Reduction of the exposure of sensitive tissues to toxic drugs.

· Site avoidance effect.

· Their surface can be modified to alter their biodistrubution and pharmacokinetics.²

Disadvantages of Liposomes:

· Leakage of encapsulated drug during storage.

· Uptake of liposomes by the reticuloendothelial system.

· Batch to batch variation .

· Difficult in large scale manufacturing and sterilization.

· Once administered, liposomes cannot be removed.

· Possibility of dumping, due to faculty administration. Production cost is high.²

Classification of Liposomes:

On their size basis and number of bilayer liposome are classified in two types viz.

· Multilamellar Vesicles(MLV)

· Unilamellar Vesicles (ULV)

Unilamellar vesicles can also classified in two types:

· Large unilamellar vesicles (LUV)

· Small unilamellar vesicles (SUV)

The liposomes size can vary from very small (0.025 mm) to large (2.5mm) vesicles.²

Importance of Liposomes in Drug Delivery System:

Pharmacokinetics- Efficiency and Toxicity:

1. Changes the absorbance and biodistubution.

2. Deliver drug in desired form.

3. Multidrug resistance.

Protection:

1. Decrease harmful side effects

2. Changes where drug accumulate in body

3. Protects drug.

Release:

1. Affect the time in which drug is released

2. Prolong time-increase duration of action and decrease administration.

Methods of Liposome Preparation:

The following methods are used for the preparation of liposomes:

1. Passive loading technique

2. Active loading technique

Passive loading technique include three different methods:

1. Mechanical dispersion method

2. Solvent dispersion method

3. Detergent solubilization method

Mechanical dispersion method:

· Technique begin with lipid solution in organic solvent and end up with lipid dispersion in water.

· Various components are combined by co-dissolving the lipids in organic solvent which is then removed by

· Film deposition under vacuum.

· After solvent removal the solid liquid mixture is hydrated using aqueous buffer.

The following are types of mechanical dispersion methods:

1. Sonication:

Sonication is also used widely for the preparation of liposomes. With this method lipid suspension are mixed using acoustic energy from either a bath or probe tip sonicator. The probe sonicator is employed for dispersion, which require high energy in small volume. Bath sonicator is more suitable for large volumes of diluted lipids.

2. French Pressure Cell:

The ultrasonic radiation degrades the lipids, other sensitive compound, macromolecules for this extruction of performed larger liposomes in a French press under very high pressure is done. This technology yields unit or oligo lamellar liposomes of size (30 – 80 mm in dia ) . Includes high cost of press that consist of electric hydraulic press and pressure cell.

3. Freeze Thaw Method:

This method is based on freezing of a unilamellar dispersion and then thawing at room temperature for 15 min. Thus the process ruptures and refuses SUV's during which the solute equilibrates between inside and outside and liposomes themselves fuse and increase in size.

Solvent Dispersion Method:

1. Ether Injection:

A solution of lipids dissolved in diethyl ether or ethylmethanol mixture is gradually injected to an aqueous solution of the material to be encapsulated at 55to 65oC under pressure. The consequent removal of ether under vacuum leads to the creation of liposomes.

2. ETHANOL INJECTION:

A lipid solution of ethanol is rapidly injected to a huge excess of buffer. The MLV are at once formed. The disadvantage of the method are that the population is heterogeneous (30 to 110 nm) liposome are very dilute the removal all ethanol is difficult because it forms into azeotrope with water.

Detergent Removal Method:

1. Dialysis:

Detergents with high CMC (10-20 mm) are used so that their removal is facilitated

E.g. bile salts-sodium cholate and sodium deoxycholate or synthetic detergents like octileglucoside. The commercial version of the dialysis system is available under the tradename LIPOREP.

2. Column Chromatography:

Phospholipid in the form of either sonicated vesicle or as dry Film at a molar ratio of 2:1 with deoxycholate form unilamellar Vesicle of 100nm on removal of deoxycholate by column Chromatography.

3. Dilution:

Upon dilution of aqueous mixed micellar solution of detergent and phospholipid with buffer the micellar size and polydispersity increase fundamentally.³

Characterization of Liposomes:

There are three main types of characterization technique of liposomes.

1. Physical Characterization:

· Vesicles size /shape /morphology

· Surface-charge /electrical potential

· Drug release

· % capture /free drug.

2. Chemical Characterization:

· Phospholipid /lipid concentration Drug concentration PH /osmolality.

· Antioxidant degradation

3. Biological Characterization:

· Sterility

· Pyrogenisity Animal toxicity.⁴

LIMITATIONS IN LIPOSOME TECHNOLOGY:

· Stability

· Gene therapy

· Sterilization

· Active targeting Lysosomal degradation

· Encapsulation efficiency.⁵

CONCLUSION:

Liposomes have been used in broad range of pharmaceutical applications. Liposomes are showing particular promise as intracellular delivery systems for anti-sense molecules, ribosomes, protein/peptides and DNA, liposomes with enhanced drug delivery to disease locations by ability of long circulation residence times are now achieving clinical acceptance. The use of liposomes in delivery of drugs and genes are promising and is sure to undergo further development in future.

REFERENCE:

1. Kant Shashi. A competitive Review on Liposomes. International Research Journal of Pharmacy. page no 10.

2. Devender Sharma. An updated Review on: Liposomes as a Drug Delivery System. Pharma Tutor. page no 50

3. Sharma Shailesh et al. Liposomes A Review. Journal of Pharmacy Research 2009, 2(7),1163-1167

4. Bangham A D, Horne R W, Glauert A M, Dingle J T, Lucy J A. Action of Saponin on Biological Cell Membranes,

5. https://images.app.goo.gl/sH1Wqbk84GhosM5f7

6. https://images.app.goo.gl/TNkDpBHhsxssHo86A

Received on 10.09.2021 Modified on 27.10.2021

Asian J. Res. Pharm. Sci. 2022; 12(1):49-51.

DOI: 10.52711/2231-5659.2022.00009