Estudos in vitro e in vivo de Annona muricata L. contra uma linhagem de Candida albicans multirresistente: atividade do extrato livre e incorporado a uma formulação a base de carbopol

Abstract

Bioactive natural products have stood out as sources of chemical diversity in the search for strategies for the discovery of new drugs. In this scenario, Annona muricata L. is traditionally used in the treatment of inflammatory, infectious and cancer diseases. However, its antifungal potential, as well as its mechanism of action, still needs further studies. The objective of this work was to evaluate the antifungal activity of the ethanolic extract of the leaves of A. muricata against a multidrug-resistant strain of Candida albicans (ATCC® 10231) and to develop a carbopol-based formulation containing the extract, aiming at the treatment of vulvovaginal candidiasis (VVC). Studies in planktonic cells were evaluated by the growth curve, cell density, mechanism of action in cell envelope and mitochondrial membrane potential. Analysis of the composition of the extracellular polymeric matrix. The in vivo assays comprised experimental VVC models testing, in addition to A. muricata, its form incorporated into carbopol. Our analyzes indicated a promising inhibitory effect of A. muricata, with the ability to reduce fungal growth, as well as the number of cells. In view of the cell envelope studies, the extract affected both the fungal membrane and the integrity of the cell wall, altering viability. Mitochondrial membrane depolarization was indicated after treatment with A. muricata. Regarding the bifilm assays, a reduction in proliferation, adhesion and polymeric matrix of C. albicans was observed. The in vivo assays demonstrated that A. muricata free and incorporated into the gel were able to reduce the fungal load, the inflammatory process and, in the presence of carbopol, an increase in mucoadhesiveness. Thus, A. muricata has antifungal potential in the treatment of C. albicans infections and the carbopol-based formulation showed the ability to be used in dermatological applications, providing its future use for the treatment of VVC. New product improvement studies will still be carried out, being necessary for a better understanding of its mechanism and physical-chemical characteristics.