Evaluation of the potential of nanostructured lipid carriers for co-encapsulation of curcumin and fluconazole dispersed in thermally-responsive hydrogels in the treatment of vulvovaginal candidiasis

Abstract

Vulvovaginal candidiasis (VVC) is a disease that affects a large part of the female population, Brazil ranking third in number of incidences of VVC in the world. The symptoms of this disease are nonspecific and are related to inflammatory processes resulting from the infection. The treatment currently available corresponds to oral and topical forms of drugs in the azole class; however, an increase in Candida sp. resistant to conventional treatments. Fluconazole is a triazole drug widely used for the treatment of VVC, but an increase in clinical isolates of candida spp. resistant to this drug. Thus, it is necessary to seek new effective therapeutic strategies. In a previous study, the synergistic potential of curcumin and fluconazole against azole-resistant C. albicans was demonstrated. Despite the potential of this association, both biomolecules have high lipophilicity, making it necessary to use a drug delivery system (DDS) to adequately explore their biological effects.Thus, the co-incorporation in nanostructured lipid carriers (CLN) demonstrates an interesting alternative, as it makes it possible to disperse them in an aqueous medium, promotes greater stability, controlled release and enables the association of its different antimycotic mechanisms, which can generate a synergism to the point of being effective even in resistant strains. However, these systems have high fluidity, requiring their dispersion in thermo-responsive gel for vaginal administration. The vaginal administration route is poorly explored in relation to oral and parenteral administration, but it stands out for not occurring first-pass metabolism and for not being an invasive route. Thus, this project seeks to evaluate the potential of CLN for co-encapsulation of curcumin and fluconazole dispersed in thermo-responsive gels in the treatment of CVV. (AU)