2.1. Aim of the work:
The aim of the present study was to investigate the feasibility of proniosomes as stable precursor for the oral drug delivery system for hydrophilic anti retroviral drug abacavir sulphate.
2.1.1. Background of Aim/Need of study:
Drugs regularly used for the management of the retroviral infection mostly exist as conventional dosage forms. The main shortcoming of these dosage forms are non specific or non targeting delivery of the drug in the site of action. By administration of the whole drug dose by conventional dosage forms, the entire amount is quickly released in to the stomach, gets absorbed into the systemic circulation and eliminated from body. Another problem of conventional dosage forms is the drug not delivered exactly into the site of action.Drug delivery systems by means of colloidalparticulate carriers such as liposomes, niosomes have distinct advantages over conventional dosage forms because the particles can act as drug containing reservoirs, and modification of the particle composition or surface can adjust the drug release rate and/or the affinity for the target site.88 However, there remain significant problems in the general application of liposomes for drug delivery.
In a dispersed aqueous system, liposomes have problems associated with degradation by hydrolysis and sedimentation, aggregation, or fusion of liposomes. The problems associated with the clinical application of liposomes include difficulties in sterilization and large-scale production.32 These problems can be evaded by proniosomes. Proniosomes are dry, free-flowing formulations of surfactant-coated carrier, which can be rehydrated by brief agitation in hot water to form a multi-lamellar noisome suspension suitable for administration by oral or other routes. In addition to that proniosomes are shown distinct advantages over conventional dosage forms in oral drug delivery.116
Proniosomes have also demonstrated the capability to deliver various antiviral agents. Proniosomes prolonging the circulation of entrapped drug and altering its organ distribution and metabolic stability and enhance the efficacy and reduce the toxicity of encapsulated antiviral agents. Thus, an important contributing factor for the development of drug resistance appears to be the inability to achieve sufficiently high concentrations of the drugs at the sites of HIV-1 infection. Proniosomes enter in
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the human body, they are recognized as the foreign bodies and easily taken up by the mononuclear phagocytic cells. HIV is present in mononuclear phagocytic cells of infected patient, so proniosomes represent suitable carriers for targeting anti-HIV drugs to the infected cells.117,118Thus, proniosomes can improve the efficacy of anti-HIV drugs and reduce their toxic effects. By considering the above advantages of Proniosomes has been selected as a carrier to deliver the abacavir sulphate.
Abacavir sulphate, the anti-HIV compound approved in 1998119 is still generally used alone or incombination with other anti retroviral agents for treatment ofAIDS and AIDS-related complex. It is the only approved antiretroviral that is active as a guanosine analog.120 Rapid diminution in plasma HIV –RNA count and quick rise in CD4 cell count has been well-known when abacavir was given to HIV infected patient.120 Abacavir has been reported to produce severe hypersensitivity reactions and adverse effects. The half life of hydrophilic abacavir sulphate is 1 to 1.5 hours.121 Marketed preparations of abacavir sulphate currently available are there in conventional dosage form. Thus current study was aimed to develop a prolonged release pronoisome formulation of abacavir sulphate for targeted delivery and to minimize the undesirable effects.
2.2. Objectives:
Dicetyl phosphate is a charged lipid used to induce negative charge to vesicles.
The first objective of these experiments was to assess the influence of negative charge inducer dicetyl phosphate in vesicle size, abacavir sulphate encapsulation and invitro release for equimolar (1:1) surfactant / cholesterol formulations.
To get the preferred characteristics of a proniosome formulation of hydrophilic drug abacavir sulphate in the presence of cholesterol, it is important to select the proper surfactant. Another objective of this study is to compare the effect of 250 μM concentration of sorbitan fatty acid esters (spans) and polyoxyethylene sorbitan fatty acid esters (tweens) surfactants in the encapsulation of water soluble drug abacavir sulphate.
The niosomes are the vesicular systems have definite advantages by means of avoiding demerits coupled with conventional dosage forms by acting as drug reservoirs and which can be expected to extend the duration of the drugs in systemic circulation with diminish the drug toxicity. However, aqueous
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dispersions of niosomes may exhibit physical instability problems such as aggregation, fusion of vesicles and hydrolysis or leaking of the encapsulated drug. Proniosomes are the dry free flowing granular niosomes and these can be hydrated instantly before use to obtain niosomal dispersion. The present work was objected to formulate and characterize the both noisomal and proniosomal formulation of abacavir sulphate to recognize the superiority of proniosomes over the conventional niosomes in all aspects in the vesicular formulation of antiretroviral drug abacavir sulphate.
To prolong the duration of action by increasing existence of drug in systemic circulation by using proniosomal formulation.
To improve efficacy and reduce the toxicity of abacavir sulphate by using proniosomal formulation.
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