Liposome: a drug carrier

INTRODUCTION

Liposome is composed of small vesicles of bilayer of phospholipids encapsulating an aqueous space ranging from about 0.03 to 10 micrometer in diameter. It can be administered parenteral, topically, by inhalation and by other route also.

HISTORY:

The word liposome derives from two Greek words: lipo (“fat”) and soma (“body”).Alec D Bangham first described liposome in 1961 which was published in 1964 in Cambridge .Alec D Bangham and Jeff Watkins wrote the paper in 1965 that effectively launched the liposome industry.

METHOD OF PREPARATION:

General method of liposome preparation include following four stages:

1. Drying down lipids from organic solvent
2. Dispersing the lipid n aqueous media
3. Purifying the resultant liposome
4. Analyzing the liposome products

Method of liposome preparation and drug loading:

1. Active loading method
2. Passive loading method

PASSIVE LOADING METHOD:

1. Mechanical dispersion method:

Dispersion of lipid in aqueous media is most variable step. Several methods are currently in use for dispersion process.

Sonification

It is the most commonly used method for dispersion of lipid, particularly for the preparation of SUVs (small unilamellar vesicles). Either a bath type sonicator or a probe sonicator under passive atmosphere is used.

In bath sonicator, the liposome dispersion is placed inside the sonicator, allowing easy control of temperature. In probe sonicator, tip of a sonicator is directly engrossed into the liposome dispersion. Bath sonication requires high energy input into lipid dispersion.

Extrusion: french pressure cell

It uses the extrusion process and pushes MLVs (multilamellar vesicles) through a small orifice to disperse the lipids.

It is more advantageous than the sonication because resulting liposome can encapsulate solutes longer than SUVs but this process requires high temperature which is difficult to control.

Freeze-thawed liposomes

In this method, the small unilamellar vesicles are frozen for short period then thawed over a long time. It leads to the formation of LUVs (large unilamellar vesicles).

Some other methods of dispersion:

• Lipid film hydration
• Micro-emulsion
• Membrane extrusion
• Dried reconstituted vesicles

      2.   Solvent dispersion method

• Ether injection (solvent vaporization)
• Ethanol injection
• Reverse phase evaporation method

      3.Detergent removal method

• Dialysis
• Gel permeation chromatography
• Dilution

Mechanism of liposome action:

There are several mechanisms which describe the action of liposome:

1. Liposome attaches to cell membrane and fused with them, releasing the content into the cell.
2. Cell takes liposome and cell membrane is incorporated with phospholipid of liposome by which trapped drug is released.
3. In phagocyte cell, the liposomes are taken up, lysosome acts on liposome, and API is released.

Advantages of liposome:

Some of the advantages of liposome are listed below.

• It provides increased efficacy and therapeutic index.
• It provides selective passive targeting to tumor tissue.
• It provides increased stability via encapsulation.
• It reduces the toxicity of the encapsulated agents.
• It has side avoidance effect.
• Pharmacological effects are improved.
• It can be used for both lipophilic and hydrophilic drugs without chemical modification.
• Liposome decreases the drug’s toxicity.

Disadvantages of liposome:

• They have tendency to be taken up by cells of the reticuloendothelial system, which may inhibit the drugs to reach the target cells.
• If the liposome is taken up by phagocyte the release of the drug would be slow.

EXAMPLE:

Name	Trade name	Uses
Liposomal amphotericin B	Abelcet	Fungal infections
Liposomal cytarabine	Depocyt	Malignant lymphomatous meningitis
Liposomal daunorubicin	DaunoXome	HIV-related Kaposi’s sarcoma
Liposomal IRIV vaccine	Inflexal V	Influenza
Rituzumab	Mabthera	Hodgkin;s lymphoma

APPLICATIONS OF LIPOSOME

In drug targeting:

The approach of drug targeting by the liposome involves the use of ligands which are tagged on the lipid vesicles. Liposome system is one of the major tools for the drug targeting.

In anti-tumor therapy:

 Use of  liposome carriers help to reduce the side effect produced by  anthracyclines which is used to stop the growth of rapidly dividing cells including cancer cells.

In fungal infection:

Liposome is used as carrier for foramphotericin B, an antifungal drug, which helps to reduce the toxicity produced by the drug.

In bacterial infection:

Several antibiotic including ribavirin, azidothymidine and acyclovir are less toxic when delivered in a liposome formulation.

In parasitic diseases:

The drug against the parasitic infection of macrophages, leishmaniasis is given through liposome because its required effective dose against the parasite is higher than toxic dose.

In topical drug delivery:

Liposome increases the permeability of skin for various drugs and reduces the chance of side effects of these drugs.

By: Sagar Baral
Central Institute of Science and Technology

New Baneshwor, Kathmandu, Nepal