Liposome as a Drug Delivery System- A Review

Suraj R. Wasankar*, Abhishek D. Deshmukh, Mohan A. Ughade, Rahul M. Burghat , Dhaval P. Gandech, Rinkesh R. Meghwani, Syed M. Faizi

Vidyabharti College of Pharmacy, Camp Road, Amravati, Maharashtra,444602,.

ABSTRACT:

A liposome is a spherical vesicle with a membrane composed of a phospholipids bilayer used to deliver drug or genetic material into a cell. Liposomes can be composed of naturally-derived phospholipids with mixed lipid chain like egg phosphatidylethonalimine or of pure components like DOPE (dioleolylphosphatidylethanolamine). There are number of the structural and nonstructural components of liposomes, major structural components of liposomes are: phospholipids and cholesterol. Liposomes are usually classified according to their lamellarity and size is MLV, LUV, SUV. Various methods used for the preparation of liposome are Passive loading techniques, Active loading technique. Therapeutic Application of Liposome are Liposome as drug/protein delivery vehicles, Liposome in antimicrobial, antifungal and antiviral therapy, Liposome in tumour therapy. Liposome in gene delivery, Liposome in immunology, etc.

KEYWORDS: Phospholipids, Cholesterol, Lamellarity, DOPE

INTRODUCTION:

Liposomes have been receiving a lot of interest as a carrier for advanced drug delivery. Liposomes were first produced in England in 1961 by Alec D. Bangham, who was studying phospholipids and blood clotting. ^[2] It was found that phospholipids combined with water immediately formed a sphere because one end of each molecule is water soluble, while the opposite end is water insoluble. Water soluble drugs added to the water were trapped inside the aggregation of hydrophobic ends; fat-soluble drugs were incorporated into the phospholipids layer.

Figure 1: Structure of Liposome

There are several mechanism by which act within and outside the body which are as follows: ^[3]

1) Liposomes attach to cellular membrane and appear to fuse with them, releasing their content in to the cell.

2) Sometimes they are taken up by the cells and their phospholipids are incorporated in to the cell membrane by which the drug trapped inside is release.

3) In the case of phagocyte cell, the liposomes are taken up, the phospholipids wall are acted upon by organelles called lysosomes and the active pharmaceutical ingredients are released. ^[4]

MECHANISM OF LIPOSOME FORMATION ^[5]

In order to understand why liposomes are formed when phospholipids are hydrated, it requires a basic understanding of physico-chemical features of phospholipids. Phospholipids are amphephatic (having affinity for both aqueous and polar moieties) molecules as they have a hydrophobic tail and a hydrophilic or polar head. In aqueous medium the molecules in self assembled structures are oriented in such a way that the polar portion of the molecule remains in contact with the polar environment and at the same time shields the non-polar part. Molecules of phosphatidylcholine (PC) are not soluble (rather dispersible) in aqueous medium in the physical chemistry sense, as in aqueous media they align themselves closely in planer bilayer sheets to minimize the unfavourable interactions between the bulk aqueous phase and long hydrocarbon fatty acyl chain. Such interactions are completely eliminated when the sheets fold over themselves to form closed, sealed and concentric vesicles. Phosphatidylcholine preferably orient to form bilayer sheets rather than micellar structures. Lipid vesicles are formed when thin lipid films or lipid cakes are hydrated and stacks of liquid crystalline bilayers become fluid and swell. The hydrated lipid sheets detach during agitation and self close to form large, multilameller vesicles (MLVs). Once these vesicles are formed, a change in the vesicle shape and morphology requires energy input in the form of sonic energy (sonication to get small unilamellar vesicles, SUVs) and mechanical energy (extrusion to get large unilamellar vesicles, LUVs).

Figure 2: Mechanism of Formation of Liposome ^[^5]

Table 1 Various marketed Formulation of Liposomes ^[5]

Product	Drug	Company
AmbisomeTM	Amphotericin B	NeXstar pharmaceutical,Inc., CO
Abeleet TM	Amphotericin B	The Liposome company, NJ
AmphocilTM	Amphotericin B	Sequus Pharmaceuticals, Inc., C.A.
DoxilTM	Doxorubacin	Sequus Pharmaceuticals, Inc., C.A.
DaunaXomeTM	Daunorubacin	NeXstar pharmaceutical, Inc., CO
MikKasomeTM	AmikacinTM	NeXstar pharmaceutical, Inc., CO
DC99TM	Doxorubacin	Liposome Co.,NJ,USA
EpaxelTM	Hepatitis A Vaccine	Swiss Serum Institute, Switzerland
ELA-MaxTM	Lidocane	Biozone Labs, CA, USA

Advantages of Liposome ^[6]

Provides selective passive targeting to tumour tissue (liposomal doxorubicin).

1. Liposome are increased efficacy and therapeutic index of drug (Actinomycin-D).

2. Liposome is increased stability via encapsulation.

3. Liposomes are biocompatible, completely biodegradable, non-toxic, flexible and nonimmunogenic for systemic and non-systemic administrations.

4. Liposome are reduction in toxicity of the encapsulated agent (Amphotericin B, Taxol).

5. Liposomes help to reduce exposure of sensitive tissues to toxic drugs.

6. Site avoidance effect.

7. Flexibility to couple with site-specific ligands to achieve active targeting.

Disadvantages of Liposome ^[6]

1. Production cost is high.

2. Leakage and fusion of encapsulated drug / molecules.

3. Sometimes phospholipid undergoes oxidation and hydrolysis like reaction.

4. Short half-life.

5. Low solubility.

6. Fewer stables.

Structural Components of Liposome^[^{6 ]}

There are number of the structural and nonstructural components of liposomes, major structural components of liposomes are:

Phospholipids

Phospholipids are the major structural component of biological membranes, where two type of phospholipids exit- Phosphodiglycerides and Sphingolipids. The most common phospholipid is phosphatidylcholine (PC) molecule. Molecule of phosphatidylcholine are not soluble in water and in aqueous media they align themselves closely in plannar bilayer sheets in order to minimize the unfavorable action between the bulk aqueous phase and long hydrocarbon fatty chain. (Fig. 4) The Glycerol containing phospholipids are most common used component of liposome formulation and represent greater than 50% of weight of lipid in biological membranes. These are derived from Phosphatidic acid.

Examples of phospholipids are:

1. Phosphatidyl choline (Lecithin) – PC

2. Phosphatidyl ethanolamine (cephalin) – PE

3. Phosphatidyl serine (PS)

4. Phosphatidyl inositol (PI)

5. Phosphatidyl Glycerol (PG)

Figure 4: Liposome Structure Formed By Phospholipids

Cholesterol ^[6]

Cholesterol dose not by itself form bilayer structure, but can be incorporated into phospholipids membranes in very high concentration up to 1:1 or even 2:1 molar ration of cholesterol to phosphatidylcholine. Cholesterol inserts into the membrane with its hydroxyl group oriented towards the aqueous surface and aliphatic chain aligent parallel to the acyl chains in the center of the bilayer. The high solubility of cholesterol in phospholipids liposome has been attributed to both hydrophobic and specific head group interaction, but there is no unequivocal evidence for the arrangement of cholesterol in the bilayer. ^[7-8]

Classification of Liposomes ^[^9]

Liposomes are usually classified according to their lamellarity and size. The following categories show the major types of liposomes (New, 1990; Philippot and Schuber, 1995):

1. Multilamellar vesicles (MLV): This population has a broad range of size distribution that occurs in a range of 100-1000 nm. The lipid composition may influence the lamellarity of these MLVs. However, the lamellarity typically varies between 5 and 20 concentric lamellae.

2. Large unilamellar vesicles (LUV): The size of these vesicles is normally up to 1000 nm and the structure consists of a single lamellae.

3. Small unilamellar vesicles (SUV): The structure normally consists of single lamellae and the diameter of this population is below 100 nm.

Method of Liposome Preparation ^[6]

Various methods used for the preparation of liposome:-

1. Passive loading techniques: Passive loading techniques include three different

methods:

a. Mechanical dispersion method

· Lipid film hydration by hand shaking, nonhand shaking or freeze drying

· Micro-emulsification

· Sonication

· French pressure cell

· Membrane extrusion

· Dried reconstituted vesicles

· Freeze-thawed liposomes

b. Solvent dispersion method

o Ether injection

o Ethanol injection

o Double emulsion vesicles

o Reverse phase evaporation vesicles

o Stable plurilamellar vesicles

c. Detergent removal method

o Detergent (cholate, alkylglycoside, Triton X-100) removal form mixed micelles

o Dialysis

o Column chromatography

o Dilution

o Reconstituted sendai virus enveloped vesicles

2. Active loading technique

(i) Detergent Dialysis

(ii) Microlluidization

(a) Proliposomes

(b) Lyophilization ^[10]

Method of Liposome Preparation: ^[12]

a) Handshaking Method

In order to produce liposome lipid molecules must be introduced into an aqueous environment. When dry lipid layer film is hydrated the lamellae swell and grow into myelin figures. Only mechanical agitation provided by vortexing, shaking, swering or pippeting causes myelin figures to break and reseal the exposed hydrophobic edges resulting in the formation of liposomes can be made by hand shaken method.

b) Sonication Method

This method is probably the most widely used method for the preparation of small Unilamellar vesicles. There are two sonication techniques:

Probe Sonication

The tip of sonicator is directly immersed into the liposome dispersion is very high in this method. The dissipation of energy at the tip results in local overheating and therefore the vessel must be immersed into an ice bath. During the sonication up to one hour more than 5% of the lipids can be de-esterify. Also, with the probe sonicator, titanium will slough off and contaminate the solution.

Bath Sonicator

The liposome dispersion in a tube is placed into a bath sonicator. Controlling the temperature of the lipid dispersion is usually easier in this method compare to sonication the dispersion directly using tip. Material being sonicated can be kept in a sterile container, unlike the probe units, or under an inert atmosphere. The lipid bilayer of the liposomes can fuse with other bilayers, thus delivering the liposome contents. By making liposomes in a solution of DNA or drug they can be delivered past lipid bilayer.

c) Reverse Phase Evaporation Method

Historically this method provided a breakthrough in liposome technology, since it allowed for the first time the preparation of liposomes with a high aqueous space-to-lipid ratio and able to entrap a large percentage of the aqueous material presented. Reverse phase evaporation is based on the formation of inverted micelles. These inverted micelles are formed upon sonication of a mixture of a buffered aqueous phase, which contains the water soluble molecules to be encapsulated into the liposomes and an organic phase in which the amphiphilic molecules are solubilized. The slow removal of the organic solvent leads to transformation of these inverted micelles into a gel like and viscous state. At a critical point in this procedure, the gel state collapse and some of the inverted micelles into a gel like and viscous state. At a critical point in this procedure, the gel state collapse and some of the inverted micelles disintegrate. The excess of phospholipids in the environment contributes to the formation of a complete bilayer around the remaining micelles, which results in formation of liposomes. Liposome made by this method can be made from various lipid formulations and have aqueous volume to lipid ratios that are four time higher than multi lamellar liposomes or hand shaken method.

d) Freeze Dried Rehydration Method

Freeze dried liposomes are formed from preformed liposomes. Very high encapsulation efficiencies even for macromolecules can be achieved using this method. During the dehydration the lipid bilayers and the material to be encapsulated into the liposomes are brought into close contact. Upon reswelling the chances for encapsulation of the adhered molecules are much higher. The rehydration is a very important step and is should be done very carefully. The aqueous phase should be added in very small portions with a micropippete to the dried materials. After each addition the tube should be vortexed thoroughly. As a general rule the total volume used for rehydration must be smaller than the starting volume of the liposome dispersion.

Solvent dispersion method ^[13]

e) Ether Injection Method

A solution of lipids dissolved in diethyl ether or ether/methanol mixture is slowly injected to an aqueous solution of the material to be encapsulated at 55-65°C or under reduced pressure. The subsequent removal of ether under vacuum leads to the formation of liposomes. The main drawbacks of the method are that the population is heterogeneous (70-190 nm) and the exposure of compounds to be encapsulated to organic solvents or high temperature.

f) Ethanol Injection Method

A lipid solution of ethanol is rapidly injected to a vast excess of buffer. The MLVs are immediately formed. The drawbacks of the method are that the population is heterogeneous (30-110 nm), liposomes are very dilute, it is difficult to remove all ethanol because it forms azeotrope with water and the possibility of various biologically active macromolecules to inactivation in the presence of even low amounts of ethanol.

g) Detergent Removal Methods

The detergents 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 were removed by dialysis . The advantages of detergent dialysis method are excellent reproducibility and production of liposome populations which are homogenous in size. The main drawback of the method is the retention of traces of detergent(s) within the liposomes. A commercial device called LIPOPREP (Diachema AG, Switzerland) which is a version of dialysis system is available for the removal of detergents. Other techniques have been used for the removal of detergents: (a) by using Gel Chromatography involving a column of Sephadex G-25, (b) by adsorption or binding of Triton X-100 (a detergent) to Bio-Beads SM-2. (c) by binding of octyl glucoside (a detergent) to Amberlite XAD-2 beads.

h) Calcium-Induced Fusion Method

This method is used to prepare LUV from acidic phospholipids. The procedure is based on the observation that calcium addition to SUV induces fusion and results in the formation of multilamellar structures in spiral configuration (Cochleate cylinders). The addition of EDTA to these preparations results in the formation of LUVs. The main advantage of this method is that macromolecules can he encapsulated under gentle conditions. The resulting liposomes are largely unilamellar, although of a heterogeneous size range. The chief disadvantage of this method is that LUVs can only be obtained from acidic phospholipids.

i) Microfluldization Method

Mayhew et al. (1984) suggested a technique of microfluidization/ microemulsification/ homogenization for the large scale manufacture of liposomes. The reduction in the size range can be achieved by recycling of the sample. The process is reproducible and yields liposomes with good aqueous phase encapsulation. Riaz and Weiner (1995) prepared liposomes consisting of egg yolk, cholesterol and brain phosphatidylserin diasodium salt (57:33:10) by this method. First MLV were prepared by these were passed through a Microluidizer (Microlluidics Corporation, Newton, MA, USA) at 40 psi inlet air pressure. The size range was 150-160 nm after 25 recylces. In the Microluidizer, the interaction of fluid streams takes place at high velocities (pressures) in a precisely definedmicrochannels which are present in an interaction chamber. In the chamber pressure reaches up to 10,000 psi this can be cause partial degradation of lipids.

j) Freeze-Thaw Method

SUVs are rapidly frozen and followed by slow thawing. The brief sonication disperses aggregated materials to LUV. The formation of unilamellar vesicles is due to the fusion of SUV during the processes of freezing and or thawing (Pick, 1981; Ohsawa et al., 1985; Liu and Yonethani, 1994). This type of fusion is strongly inhibited by increasing the ionic strength of the medium and by increasing the phospholipid concentration.The encapsulation efficiencies from 20 to 30% were obtained.

Table 2 Liposome Characterization

CHARACTERIZATION PARAMETER

ANALYTICAL METHODS/INSTRUMENTATION

Chemical Characterization

Concentration

Phospholipids

Cholesterol

Drug

Phosphoipid

Peroxidation Hydrolisis

Cholesterol autooxidation

Antioxidatin degradation

Osmolarity

Bsrlett /Stewart assay, HPLC

Cholesterol oxidase assay, HPLC

Methods as in individual monograph

UV absorbance, TBA, Iodometric, GLC

HPLC,TLC, Fatty acid concentration

HPLC,TLC

HPLC,TLCPH Meter

Osmometer

Physical Characterization

Vesicles

Size and Surface

Morphology

Size Distribution

Surface charge

Electric surface potential and pH

Lamellarity

Phase behavior

% Entrapment efficiency

Drug release

TEM, Freeze fracture electron microscope

DLS, Zetasizer, TEM,PCR, Gel permeation, Exclusion

Free flow electrophoresis

Zeta potential measurement , pH probes

SAXS, NMR, Freeze fracture electron microscope

DSC, Freeze fracture electron microscope

Minicolumn centrifugation, gel exclusion, ion exchange , protamine aggregation , redioleblling

Diffusion

Biological Characterization

Sterility

Pyrogenicity

Animal toxicity

Aerobic or anaerobic culture

LAL test

Monitoring survival rates , Histophathology.

Table 3: Liposome in the Science

Discipline	Application
Mathematics	Topology of two dimensional surfaces in 3D governed only by bilayer elasticity
Physics	Aggregation behavior , fractals,soft and high strength materials
Biophysics	Permeability, phase transitions in two dimension, photophysics
Physical Chemistry	Colloid behavior in a system of well defined physical characteristic,inter and intra aggregat forces,DLVO
Chemistry	Photochemistry, artificial photosynthesis , catalysis, micro-compartmentalization
Biochemistry	Reconstitution of membrane proteins in to artificial membranes
Biology	Model biological membranes, cell function, fusion, recognition
Pharmaceutics	Studies of drug action
Medicines	Drug delivery and medical diagnostics, gene therapy

Storage of liposomes: ^[15]

Freeze-drying Liposome dispersions are potentially prone to hydrolytic degradation and leakage. Hence, it is desirable to freeze-dry the suspension to a powder and store in this dried form. The powder can be reconstituted to an aqueous suspension immediately before use. By doing so, SUVs may be converted to MLVs dispersion upon rehydration. Addition of a carbohydrate (trehalose) during freeze-drying prevents fusion and leakage of the vesicles.

Stability of Liposomes ^[16]

a) Physical and Chemical Stability

Cholesterol and phospholipids containing unsaturated fatty acids undergo oxidation. One solution to this problem is to use phospholipids which contain saturated fatty acids. Synthetic saturated lecithins provide a good alternative to egg or soybean lecithin.

Lecithin undergoes hydrolysis to give lysolecithin and other degradation products. The presence of lysolecithin in lipid bilayers greatly enhance the permeability of liposomes. Therefore, it is important to start with phospholipids which are free of lysolecithin (also of any phospholipases). The rate of hydrolysis of distearoylphosphatidylcholine in aqueous solution at 70°C was found to be dependent on pH 6.5.

Freeze drying (lyophilizalion) can be useful in some cases to solve long term stability problems of liposomes. On reconstitution (rehydration) most of drug remains within liposomes. It has been shown that liposomes when freeze dried in the presence of trehalose (a sugar) retained as such as a 100% of their contents.

Another way to increase stability of liposomes is to use synthetic phospholipids which polymerize on exposure to UV light (Hayward et al., 1936). To solve long term stability problems, recently 'Proliposomes" were prepared using sorbitol and methanolic solution of phospholipids. These are dry powders containing water soluble compound/drug coated by phospholipids. They give liposomes on hydration above the gel-liquid crystalline phase transition temperature.

An increase in physical stability of liposomes can be achieved by increasing amount of charge on liposomes. For example, Frokjaer et al. (1982) reported an increase in physical stability against aggregation and fusion by decreasing the ionic strength and increasing surface charge density of liposomes consisting of phosphatidylcholine and phospholidylserine. In vivo, the surface large density has been found to influence the distribution of liposomes (Rahman et al., 1980).

b) Stability in Biological Fluids

The stability of liposomes in the circulation is of great interest when they are to be applied as intravenous drug carriers. This is a well established fact that the liposomes are generally unable to retain their entraped substances when incubated with blood or plasma. Generally MLV are most stable since only a portion of the phospholipid is exposed to the attach and SUV are the least stable because of the stress imposed by their curvature. The incorporation of cholesterol sometimes increases the stability of liposomes in the presence of plasma. Senior and Gregoriadis (1982) studied the stability of SUV in mouse serum at 37°C. Liposomes composed of egg lecithin, dioleylphosphatidylcholine or sphingomyelin became rapidly permeable to entraped carboxyfluorescein (CF) but the incorporation of cholesterol in the liposomes reduced CF leakage. Further it was found that the stability of liposomes in plasma can be in-creased by using saturated phospholipids but this stability was dependent on the gel-liquid crystalline phase transition temperature of the phospholipid(s) present in the liposomes.

It has been found that proteins particularly high density lipoprotein (HDL) are mainly responsible for the increase in permeability of liposomes. The lipid from liposomes are transferred to the protein which in turn results in an enhanced leakage of the entraped solute probable due to the formation of pores in the bilayer(s) (Kirby and Gregoriadis, 1981). Further transfer of lipid occurs from liposomes to plasma membranes and vice versa is also true (Ostro, 1987). Agarwal et al. (1986) reported that the transfer of phospholipid from liposomes to HDL could be prevented by using a phosphatidylcholine analogue.

The permeability studies were made on liposomes made from polymerizable diacetylenic phospholipids in the presence of plasma. The incubation of liposomes containing Cu identical chain PC showed high permeability of monomeric vesicles to both carboxyfluorescein and H-inulin in plasma. While permeability of polymerized Cu identical chain PC liposomes was unaffected in the presence of plasma, with vesicles retaining most of their entraped 3H-inulin after 50 hours. These findings suggest that the polymeric liposomes have resistance against the destructive actions of plasma components particularly HDL (Freeman et al., 1987). The stability of liposomes in gastrointestinal tract is very important if they are to be used as drug carrier by the oral route. A lot research has been done to study the stability of liposomes to maintain their integrity against enzymes found in the GIT, bile salts and gastric acidity. The pancreatic lipase was capable of degrading naturally occurring phospholipids.

It has been found that liposomes containing short chain fatty acids were more stable against destructive action of lipase (Dapergolas and Gregoriadis, 1977). Phospholipase Al and A2 cause the formation of lysophosphatidylcholine which then induced lysis of the liposomes when these were incubated at or near transition temperature of the phospholipid (Horlos et al., 1977).

Application of liposomes^[^6]

Therapeutic Application of Liposome

1. Liposome as drug/protein delivery vehicles

• Controlled and sustained drug release

• Enhanced drug solubilization

• Altered pharmacokinetics and biodistribution

• Enzyme replacement therapy and biodistribution

•Enzyme replacement therapy and lysosomal storage disorders

2. Liposome in antimicrobial, antifungal and antiviral therapy

• Liposomal drugs

• Liposomal biological response modifiers

3. Liposome in tumour therapy

• Carrier of small cytotoxic molecules

• Vehicle for macromolecules as cytokines or genes

4. Liposome in gene delivery

• Gene and antisense therapy

• Genetic (DNA) vaccination

5. Liposome in immunology

• Immunoadjuvant

• Immunomodulator

6. Liposome in the Science^[^16]

7. Liposome in the Pharmaceutical Industry^[^17]

Table 4: Liposome in the Pharmaceutical Industry

Liposome Utility	Current Application	Disease States Treated
Solubilzation	Amphotericin B, Minoxidil	Fungal infections
Site-Avoidance	Amphotericin B- reduced nephrotoxicity, Doxorubicin-decreased cardiotoxicity	Fungal infections , Cancer
Sustained Release	Systemic antineoplastic drugs, hormones, Corticosteroids, drug depot in lungs	Cancer, biotherapeutics
Drug Protection	Cytosine arabinoside, interleukins	Cancer, etc
RES targeting	Immunododulators, vaccines, antimalarials, Macrophage- located diseases	Cancer, MAI, tropical parasites
Specific Targeting	Cells bearing specific antigens	Wide therapeutic applicability
Extravasations’	Leaky vasculator of tumours, inflammation, infections	Cancer, bacterial infections
Accumulation	Prostaglandins	Cardiovascular diseases
Enhanced Permeation	Topical vesicles	Dermatology
Drug Depot	Lungs, subcutaneous, intra muscular, ocular	Wide therapeutic applicability

Literature Survey

Sr. no	Drug	Excipient	Methods	Optimized formula in mg	Conclusion
1	Diclofenac Sodium	Soya lecithin, cholesterol	Film hydration method	Soya:chol:drug 100:15:25,50,75	Increased drug accumulation in the skin
2	Tacrolimus	Soya lecithin, cholesterol	Film hydration method	TAc:soya:chol 10:100:30	Higher rate of drug transfer across the skin
3	Chloramphenicol	Egg pc or egg pg	Proliposome , Polyole dilution method	Epc:Chloram-9:1 Epg:chloram-20:1	--------------
4	Dexamethasone and diclofenac sodium	Phospholipon 90G DPPE	Film hydration method	Not given	Combination give better effect on osteoarthrites
5	Flurbiprofen	Soya pc,DPPC Cholesterol,Soya lecithin,	Film hydration method	Drug-10mg,pc-100mg Chol-12mg	Optimum amount of cholesterol increased encapsulation efficiency
6	tetracain	Soya lecithin, cholesterol	Film hydration method	Soya b-7%,Chole-1%,tetra-2%	Local anesthetic duration increased
7	Nimesulide	DPPc, Chole, Stearic Acid	Ethanol Injection And Film hydration method	DPPc-40mg,Soya-10m Chol-40mg,Drug-10mg	Film Hydration method is better than ethanol inj method
8	Nicotin	Egglecithin,Sorbitol,Cho,Diacytilphosphate	Film hydration method Proliposome ,	Egg pc-50mg,Chol-50mg Diacytil Phos-10mg	Larger size of lipo was obtained
9	Flucanazole	Soya lecithin, cholesterol Tocopherol acetae	Film hydration method	Drug:soya:chol 2:10:1	Tocopherol provide stability of liposome
10	Ketoconazole	Soya lecithin, cholesterol Tocopherol acetae	Film hydration method	Not given	Liposomal gel increased retaintion time on skin
11	Tamoxifen	Soya lecithin, cholesterol Diacytil phosphate,sterilamine	Film hydration method	Tam:Pc:Chol 10:100:50	Soya gives better result than sterilamine
12	Lidocain Hcl	Soya lecithin, cholesterol	Film hydration method	Not given	Gives better effect than conventional formulation
13	Repavacain and benzocain	EPC,Chol<tocopherol	Film hydration method	EPC:Chol:Toco $:3:0.007	Gives better effect than conventional formulation
14	Dithronol	Phospholipon 90g chol, DCP,BHT	Film hydration method	Drug:Pc:Chlo 1:6:6	Duration of treatmentwas reduced
15	Acyclovir	PC,PG,SA	Polyole dilution method	Not given	This method gives better acv encapsulation efficiency

CONCLUSION

Twenty five year of research into the use of liposome in drug delivery. Liposomes areone of the unique drug delivery system, which can be of potential use in controlling and targeting drug delivery.Liposomes are administrated orally, parenterally and topically as well as used in cosmetic and hair technologies, sustained release formulations, diagnostic purpose and as good carriers in gene delivery various drugs with liposomal delivery systems have been approved. Nowadays liposomes are used as versatile carriers for targeted delivery of drug.

This review showed that liposomes have been prepared from a variety of synthetic and naturally occurring phospholipids and generally contain cholesterol as membrane stabiliser. Several methods of preparing liposomes were identified, which could influence the particle structure, degree of drug entrapment and leakage of the liposomes. It was also identified that there are improved pharmacokinetic properties with liposomal drugs compared to the free drugs. Furthermore, liposomes are tools for drug targeting in certain biomedical situations (e.g., cancer) and for reducing the incidence of dose related drug toxicity. Instability of the preparations is a problem, which is yet to be overcome before full commercialization of the process can be realized.

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Received on 17.01.2012

Modified on 29.01.2012

Accepted on 06.04.2012

Research Journal of Pharmaceutical Dosage Forms and Technology. 4(2): March-April 2012, 104-112