Clinical Management Of Psoriasis Using 0.25% Niosomal Methotrexate Gel: A Placebo Controlled Double Blind Study

摘要

In the formulation of topical dosage forms, more attention has been devoted to new structures, which can ensure either adequate localization of drug within the skin to enhance the local effect or can increase the penetration through the stratum corneum. For these purposes vesicular systems such as niosomes and liposomes have been investigated by several groups. Drug delivery systems using colloidal particulate carriers such as liposomes or niosomes have distinct advantages over conventional dosage forms because the particles can act as drug containing reservoirs. Methotrexate (MTX) is used in psoriasis as a systemic therapy with lot of adverse effects. A novel sustained release niosomal 0.25% MTX using a polymer chitosan administered once daily for 12 weeks. It was compared with placebo gel and plain MTX 0.25% gel for the treatment of different types of psoriasis, especially palmoplantar psoriasis.30 patients were enrolled for study. They were divided randomly in to three groups of 10 patients for each formulation. The patients with 25% or less than 25% psoriatic lesions were included for the study.The results are calculated using PASI scoring. Changes in the disease signs and symptoms indicated that both agents have anti psoriatic activity but not with placebo gel. However lesions treated with Niosomal chitosan-MTX formulation showed marked improvement in comparison to plain MTX and placebo gel inspite of twice a day application. Few patients experienced mild adverse events. No clinically significant changes in blood or other lab parameters were seen.The findings suggest that the 0.25% niosomal MTX in chitosan gel exhibited beneficial effect in psoriasis and did not exert any systemic toxicity. Background Psoriasis is a common noninfectious chronic inflammatory skin disorder characterized by well defined, distinctive erythematous plaques that produce adherent silvery white scales which may cause bleeding points when removed (auspitz's sign). Psoriasis may flare up at any cutaneous surface but most frequent sites are the extensor surfaces of the elbows and knees, scalp and sacral areas1. Methotrexate (MTX) is frequently used orally in the treatment for severe, recalcitrant psoriasis. Although effective, MTX has the potential to induce hepatotoxicity, bone marrow suppression, and other adverse effects, thus limiting its use for systemic therapy. To minimize the systemic exposure and toxicity associated with orally administered MTX, topical MTX formulations containing Azone (laurocapram), a skin penetration enhancer are being developed and evaluated 2 .Earlier study of MTX (0.1,0.5,and1%) in Azone formulation produces a 50% or greater improvement in psoriatic patients following 6 weeks twice daily application. Inorder to have better skin penetration and also sustained effect to improve the patient compliance a novel drug delivery using niosomal methotrexate incorporated in chitosan polymer in the form of gels were used as once daily application 3.Niosomes or non-ionic surfactant vesicles are now widely studied as an alternative to liposomes and produces sustained release of drug topically. An increasing number of non-ionic surfactants have been found to form vesicles capable of entrapping hydrophobic and hydrophilic solutes. These non-ionic surfactant vesicles are regarded either as inexpensive alternatives, of non-biological origin, to liposomes, or perhaps in vivo as a carrier system to carry drug molecules like liposomes 4,5.Chitosan, a natural polysaccharide, is being widely used as a pharmaceutical excipient. It is obtained by the partial deacetylation of chitin, the second most abundant natural polymer. The presence of a number of amino groups permit chitosan to chemically react with anionic systems, thereby resulting in alteration of physicochemical characteristics of such combinations. The polymer has also been investigated as a potential adjuvant for swellable controlled drug delivery systems. Chitosan exhibits myriad b