Potencial antifúngico e tecnológico de Mitracarpus frigidus: Desenvolvimento de biomateriais poliméricos aplicados à esporotricose

Abstract

Sporotrichosis is a subcutaneous mycosis caused by species of the genus Sporothrix, especially Sporothrix brasiliensis due to its high virulence and epidemiological importance in Brazil. Therapeutic limitations associated with currently used antifungal agents, including prolonged treatment periods, toxicity, and reduced fungal susceptibility, reinforce the need to investigate new therapeutic strategies. In this context, natural products and polymeric biomaterials have attracted attention due to their antifungal, anti-inflammatory, and technological potential. Therefore, this study aimed to chemically characterize the ethanolic extract of Mitracarpus frigidus (MFE), evaluate its antifungal activity against Sporothrix species, and develop chitosan-based polymeric films incorporated with the plant extract for topical application in sporotrichosis. The extract was characterized by UPLC-QTOF-MS/MS, revealing the presence of phenolic compounds, flavonoids, and triterpenes. MFE exhibited moderate antifungal activity against clinical and reference strains of Sporothrix spp. (MIC of 500 µg/mL), in addition to reducing the adhesion (>80% for S. schenckii and S. brasiliensis) and proliferation phases of fungal biofilms (52.56% for S. schenckii and 23.75% for S. brasiliensis). Mechanism of action analyses demonstrated increased intracellular production of reactive oxygen species and alterations in mitochondrial membrane potential, suggesting interference with essential cellular processes. The extract also showed low cytotoxicity, maintaining cell viability above 70% in L929 fibroblasts and peritoneal macrophages at concentrations up to 150 µg/mL, in addition to anti-inflammatory activity through the reduction of nitric oxide and reactive oxygen species production. In parallel, chitosan-based polymeric films containing MFE were developed and exhibited suitable physicochemical, mechanical, and microstructural properties for topical application, as well as antifungal activity, with inhibition rates above 90% against different clinical and standardized strains of Sporothrix spp., antibiofilm activity, antiinflammatory effects with reductions greater than 40% in nitric oxide production in formulations containing higher extract concentrations, and in vitro wound healing potential. The results demonstrated that M. frigidusrepresents a promising source of bioactive compounds and that its incorporation into polymeric biomaterials may constitute an innovative strategy for the development of topical formulations for sporotrichosis treatment.