Liposome in Drug delivery system

Abhijit Ray

HOD, Department of Biotechnology, Raipur Institute of Technology, Raipur (CG)

*Corresponding Author E-mail: abhijitray_2001@yahoo.com

ABSTRACT:

Today, clinical medicine possesses an extremely long list of different pharmaceutical products and every year many new drugs are added to the list with the understanding of molecular mechanisms of diseases. Scientists and physicians are never satisfied only with a favorable drug action against the disease under treatment. The task of avoiding undesirable drug actions on normal organs and tissues and minimizing side effects of the therapy is very important. Thus, screening of biologically active compounds became necessary, permitting the choice of drug with selective action on the appropriate organs or tissues. A liposome is an artificially prepared vesicle composed of a lipid bilayer. The liposome can be used as a vehicle for administration of nutrients and pharmaceutical drugs. Liposomes can be prepared by disrupting biological membranes such as by sonication.

Liposomes are composed of natural phospholipids, and may also contain mixed lipid chains with surfactant properties. A liposome design may employ surface ligands for attaching to unhealthy tissue. The major types of liposomes are the multilamellar vesicle (MLV), the small unilamellarvesicle (SUV), and the large unilamellar vesicle (LUV).

KEYWORDS: Liposomes, drug delivery, target therapy, encapsulation.

INTRODUCTION:

Liposomes are sub-micron particles that are finding important applications in fields such as biotechnology (in applications like siRNA delivery, antibody delivery), cosmetology (emulsions and creams etc.) and the pharmaceutical industry (chemotherapeutic delivery, altering the PK/PD of drug). Liposomes are composed of phospholipids that have a polar end attached to a non-polar chain. When these phospholipids are introduced into an aqueous medium, they self-assemble into bilayer vesicles with the polar ends facing the aqueous medium and non-polar ends forming a bilayer. In pharmaceutical applications the active molecule (drug) is usually incorporated into the liposome either into the hydrophilic pocket or sandwiched between the bilayers depending on the hydrophilicity or lipophilicity of the drug. Chemotherapeutics such as Doxorubicin and Paciltaxel have been used to treat cancers of various kinds for over two decades.

The main disadvantage with these or any other chemotherapeutic drug is their inability to differentiate between a normal cell and a cancer cell. This leads to unwanted side effects such as loss of hair, stomach ulcers and loss in body weight. Drug delivery systems or targeting systems that would channel these and other therapeutics to the area of interest (tumors etc.) have garnered tremendous interest.

DOXIL, a reformulated version of Doxorubicin, was one of the first drugs to be approved that is delivered using a liposome. The Doxorubicin drug lies within the hydrophilic pocket of a liposome coated with PEG (polyethylene glycol) to evade detection and destruction by the immune system. The PEG coating improves the stability and lengthens the half-life in circulation. A PEG coated liposome is often referred to as a sterically enhanced or stealth liposome. For solid tumors, liposomes are of particular interest because of their easy manipulation and optimum size. It has been known for some time that the tumor areas have leaky vasculature and poor lymphatic drainage. This can be used as a targeting tool with what has been described as Enhanced Permeation and Retention effect (EPR). This refers to the permeation and retention of molecules of sizes 50 to 150 nm in to the tumor area. Hence size measurement is of prime most importance in liposomal drug delivery systems.

Liposomes were first described by British haematologist Dr Alec D Bangham (Bangham

and Horne1964; Horne et al., 1963; Bangham et al., 1962) in 1961 at the Babraham Institute, in Cambridge. It were discovered when Bangham and R. W. Horne were testing the institute's new electron microscope by adding negative stain to dry phospholipids. The resemblance to the plasmalemma was obvious, and the microscope pictures served as the first real evidence for the cell membrane being a bilayer lipid structure. The word liposome derives from two Greek words: lipo ("fat") and soma ("body"); it is so named because its composition is primarily of phospholipid.

Liposomes are lyotropic liquid crystals composed of relatively biocompatible and biodegradable materials and consist of an aqueous core entrapped by one or more bilayers of natural and/or synthetic lipids. Drugs with widely varying lipophilic nature can be encapsulated in liposomes either in the phospholipid bilayer, in the entrapped aqueous core or at the bilayer interface. Reformulation of drugs in liposomes has provided an opportunity to enhance the therapeutic indices of various agents mainly through the alteration of bio distribution. They are versatile drug carriers, which can be used to control retention of entrapped drugs in the presence of biological fluids, controlled vesicle residence in the systemic circulation or other compartments in the body and enhanced vesicle uptake by target cells (Pozanansky and Juliano 1984). Liposomes composed of natural lipids are biodegradable, biologically inert, weakly immunogenic (Gregoriadis and Florence 1993; van Rooijen and van Nieuwmegen 1980), produce no antigenic or pyrogenic reactions and possess limited intrinsic toxicity (Campbell 1983). Therefore, drugs encapsulated in liposomes are expected to be transported without rapid degradation and minimum side effects to the recipients. Moreover, efforts have been made to assess the specificity of drug carriers to the target organs, cells or compartments within the cells (Gregoriadis 1977). Liposomes are better suited for assessing their targetable properties because of the ease of modifying their surface when compared to other drug carriers such as nanoparticles (Grislain et al., 1983; Illum et al., 1983) and microemulsions (Hashida et al., 1977; Mizushima et al., 1982). Many approaches have been attempted to achieve targetable properties, including noncovalent association of cell specific antibodies with liposomes (Gregoriadis and Neerunjun 1975), coating of liposomes with heat aggregated immunoglobulins M (IgM) (Weissmann et al., 1975), covalent attachment of poly and monoclonal antibodies to the liposomes, glycoprotein bearing liposomes (Banuo et al., 1983) and natural (Szoka and Mayhew 1983; Spanzer and Scherphof 1983; Soriano et al., 1983) and synthetic glycolipid containing liposomes. The compounds entrapped into the liposomes are protected from the action of external media, particularly enzymes (Chaize et al., 2004) and inhibitors. Moreover, liposomes afford a unique opportunity to deliver the drugs into cells by fusion or endocytosis mechanism and practically any drug can be entrapped into liposomes irrespective of its solubility.