Abstract

INTRODUCTION

Liposomes are small synthetic vesicles of spherical shape which can be developed from two major materials cholesterol and natural non-toxic phospholipids. Its hydrophobic and hydrophilic nature and are promising systems for drug delivery. In 1965, some researchers published the primary description of swollen phospholipid systems. Within a couple of years, a spread of enclosed phospholipid bilayer structures consisting of single bilayers, initially 'Bangosomes' then 'liposomes', were described. It has been expressed that phospholipids impulsively form closed structures when they are hydrated in aqueous solutions. Such vesicles that have one or more phospholipid bilayer membranes can transport aqueous or lipid drugs, counting on the character of these drugs. The lipid used to make liposomes belong to both hydrophilic and hydrophobic nature show (amphipathic nature) in aqueous media, their thermodynamic phase properties and self-assembling characteristics impression entropically focused attachment of their hydrophobic sections into spherical bilayers. Those layers are referred to as lamellae. Liposomes are used to improve the therapeutic index of both new and old drugs by modifying drug absorption, reducing metabolism, long biological half-life, or decrease toxicity. Drug distribution is then controlled primary properties of the carrier and not by the physicochemical character of the drug substance only. Lipids forming liposomes also maybe both types natural or synthetic, and liposome ingredients aren't particular of lipids, new generation liposomes also can be constituted from polymers. The composed liposomes may be natural or synthetic lipids or polymers, liposomes are biocompatible and biodegradable making them suitable for a different type of biomedical research. This feature, including biocompatibility and biodegradability both, makes it very useful, attractive as drug delivery vehicles 1, 2, 3, 4, 5, 6.

MECHANISM OF FORMATION OF LIPOSOME

A phospholipid is a backbone for the formulation of liposomes. A liposome may be a solution and core surrounded by a hydrophobic membrane, within the sort of a lipid bilayer, hydrophilic solutes dissolved within the core cannot readily pass through the bilayer. Hydrophobic substances are associated with the bilayer. To deliver the molecules to a site of action, the lipid bilayer can fuse with other bilayers like a cell membrane. This is a complex and non-spontaneous event. Liposomes are used as models for artificial cells. Liposomes can also be designed to deliver drugs in a different types of ways. Liposomes to implant low or high pH may be built such as dissolved aqueous drugs will be charged in the solution. The pH is naturally neutralized inside the liposome, the drug will be neutralized, make free it to freely undergo a membrane. These liposomes work to deliver drugs by diffusion instead of by direct cell fusion. A similar approach an often exploited within the biodetoxification of medicine by injecting empty liposomes with a transmembrane pH gradient. In this case, the vesicles act as sinks to scrub the drug in the blood circulation and prevent its toxic effect. Another strategy for liposome drug delivery is to focus on endocytosis events. These liposomes could also be digested while within the macrophage's phagosome, thus releasing its drug. Liposomes also fitted with opsonin and ligands to activate endocytosis into the other type of cells. The use of liposomes for the transformation or transfection of DNA into a number cell is known as liposome transfection. liposomes are often used as carriers for the delivery of dyes to textiles 7, 8, 9.

ADVANTAGES OF LIPOSOMES

• Provide sustained release.

• Nonionic

• Liposomes are used as targeted drug delivery or site-specific drug delivery.

• Stabilization of entrapped drug from a hostile environment.

• Can carry both water and lipid-soluble drug.

• The biodegradable drug can be stabilized from oxidation.

• Improve protein stabilization.

• Controlled hydration

• Can be administered through various routes.

• Alter pharmacokinetics and pharmacodynamics.

• Liposomes proposed various advantages in delivering genes to cells.

• Liposomes have both negatively and positively charged molecules.

• Liposomes offer protection of DNA from degradative processes.

• Liposomes may be carries large flinders of DNA, possibly as a chromosome.

• Liposomes are targeted to specific cells or tissues.

• Liposomes are a more effective and therapeutic index of drugs.

• Liposomes help reduces the exposure of sensitive tissue to the toxic drug.

• Springiness to couple with site-specific ligands to obtain active targeting 10, 11.

DISADVANTAGES OF LIPOSOMES

• Production cost is high.

• Leakage and fusion of encapsulated drug and/or molecules.

• Sometimes phospholipid undergoes oxidation and hydrolysis-like reactions.

• Short half-life.

• Low solubility.

• Fewer stables.

• Quick uptake by cells R.E.S.

• Batch to batch variation.

• Difficult in large-scale manufacturing and sterilization.

• Once administered, liposomes cannot be removed.

• The allergic reaction may occur with liposomal constituents.

• Possibility of dumping, due to faulty administration.

• Rapid clearance from circulation due to uptake 10, 11.

LIPOSOMAL DRUG DELIVERY SYSTEM

Structural and design considerations for liposomal drug delivery. Liposomal surface functionalized to provided deception through PEGylation promote receptor-mediated endocytosis by using targeting ligands like antibodies, peptides, proteins, carbohydrates, and different small molecules. PEGylation enlarges liposomal circulation half-life in vivo by decrease clearance, immune recognition, and the non-specific absorption of serum proteins. PEGylation density composes its structure at the liposome surface, with a density below 9-10% appropriate to a fungus-like circular structure and those above 9-10% adopting a more tough, extended, brush-like morphology. Diagnostics and chemotherapy may be encapsulated into the aquatic lumen, consolidated into the lipid bilayer, or conjugated to the liposome surface.

TYPES OF LIPOSOME

The liposomes have a size from very small (0.025 μm) to large (2.5 μm) vesicles. Moreover, liposomes may have one or bilayer membranes. The liposomal vesicle size is a rapid parameter in determining the circulation half-life of liposomes, and both size and number of bilayers affect the amount of drug encapsulation in the liposomes 12.

Based on their size and number of bilayers, liposomes can also be classified into two categories:

• Multilamellar vesicles (MLV)

• Unilamellar vesicles (ULV)

Unilamellar vesicles classified into two categories

• Large unilamellar vesicles (LUV)

• Small unilamellar vesicles (SUV)

METHODS OF PREPARATION OF LIPOSOMES 13, 14

General methods of preparation

• Drying down lipids from organic solvent

• Dispersing the lipid in aqueous media

• Purifying the resultant liposome

• Analyzing the final product

Methods of liposomes preparation and drug loading

• Passive loading techniques

• Active loading technique

Passive loading techniques include three different methods

• Mechanical dispersion method

• Solvent dispersion method

• Detergent removal method (removal of non-encapsulated material)

Mechanical dispersion method

• Sonication

• French pressure cell: extrusion

• Freeze-thawed liposomes

• Lipid film hydration by handshaking, non-hand shaking, or freeze-drying

• Micro-emulsification

• Membrane extrusion

• Dried reconstituted vesicles

EVALUATION OF LIPOSOMES

Liposomes are ready by various methods/techniques are to be evaluated for physical, chemical, and biological properties, as these influence the behavior of liposomes in vivo.

PHYSICAL PROPERTIES

Particle size

These can be determined by the following method.

a) Laser light scattering

b) Transmission electron microscopySurface charge

The passive, negative or natural charge on the surface of the liposomes is due to the composition is the head groups. The surface charge of liposomes governs the kinetics and extent of distribution in vivo, also as interaction with the target cells.The method involved within the measurement of surface charge is predicated on free-flow electrophoresis of MLVs. It utilizes a cellulose ester plate dipped in sodium borate buffer of pH 8.8. About moles of lipid samples are applied onto the plate, which is then subjected to electrophoresis at 4'C for 30 mins. The liposomes get bifurcated counting on their surface charge.Percent drug encapsulated

The quantity of drugs entrapped within the liposomes helps to estimate the behavior of the drug in a biological system. The %age of drug encapsulation is done by first separating the free drug friction from the encapsulated drug fraction.The encapsulated drug fraction is then made to lack the liposomes into an aqueous solution using suitable detergents.

The methods want to separate the free drug from the sample are:

a) Mini column centrifugation method

b) Protamine aggregates methodPhase behavior

At the transition, temperature liposomes undergo a reversible phase transition. The TC is that the indication of stability permeability and also indicates the region of drug entrapment. It is done by DSC.Drug release rate

The rate of drug release from the liposomes can be determined by in vivo assays which help to predict the pharmacokinetics and bioavailability of the drug. However, in vivo studies are found to be more complete. Liposomes encapsulating the tracer insulin are employed for the study. This insulin is preferred because it is released only within the ECF and undergoes rapid renal excretion of the face tracer coupled to the degradation rate constant o the tracer released from the liposomes.

CHEMICAL PROPERTIES

APPLICATION OF LIPOSOMES

CONCLUSION

Liposomes have been recognized as extremely useful carrier systems for targeted drug delivery. Liposomes are used in broad areas of pharmaceutical applications. It showing particular promise as an intracellular delivery system for antisense molecules, DNA, and also protein and peptides. It also promotes targeting the particular disease cells within the disease site. Finally, liposomal drugs exhibits reduce toxicities. And its enhanced drug delivery to disease location along with long circulation residence time, are now achieving clinical acceptance. Many liposomal products are already in the market and many are under clinical trial to get approval.