Desenvolvimento de hidrogéis mucoadesivos contendo nanocápsulas catiônicas de clotrimazol para o tratamento da candidíase vulvovaginal

Abstract

This study aimed the development of a novel formulation for the treatment of vulvovaginal candidiasis. Polymeric nanocapsules of Eudragit® RS100 were used as a clotrimazole carrier system and evaluated for their mucoadhesive potential by mucin particle method. The change of the mean diameter particle (142 ± 5 nm to 195 ± 9 nm) and the zeta potential inversion showed that the mucoadhesion is attributed to the cationic character of the polymer. Nanocapsules suspension were incorporated into hydrogels, which have prior mucoadhesion properties, in order to obtain a dosage form for vaginal application. The mucoadhesive potential conferred for polymers was demonstrated by the falling liquid film method, evaluating the quantity of formulation adhered in the mucin gel or cow vaginal mucosa. The Pemulen® TR1 hydrogels containing the nanocapsules of Eudragit® RS100 and Pullulan (at 3% concentration) showed about 55% of retention the drug in the mucosa layer; however, hydrogel containing nanocapsules without Pullulan had only 38% of the retained drug. Regarding of hydrogels containing the drug non-encapsulated, it was observed around 24% of the formulation. Thus, it was confirmed the increased of mucoadhesion due the synergism of the polymers used. In relation to physicochemical properties, formulations associating the two mucoadhesive polymers, Pemulen® TR1 and Pullulan, the hydrogels showed appropriate characteristics, similar aspect to a gel-cream, pH in the acidic range (around 5), nanometric particles size (287 ± 22 nm), clotrimazole content close to 1 mg/g and appropriated spreadability. These characteristics remained stable during the storage time (60 days). Additionally, the study of permeation/penetration was evaluated using Franz diffusion cells, and such the cow vaginal mucosal as barrier. The results obtained showed that, semisolid formulations (hydrogel) containing the nanocapsules suspensions and the combination of Pemulen®TR1 and Pullulan, demonstrated better technological results for effective treatment against the superficial infections such as candidiasis, in relation to the same formulation containing the drug not-associate, as there was an increased retention of the drug on the mucosal surface, in addition to not detected in the receptor medium. Thus, the formulations developed showed promise for the treatment of vulvovaginal candidiasis.