Avaliação, in vitro, de inibidores da bomba de prótons encapsulados em micropartículas de quitosana frente a cepas de Sporothrix spp.

Abstract

Sporotrichosis is a subcutaneous mycosis that affects humans and warm-blooded mammals, caused by dimorphic fungi belonging to the Sporothrix spp. clinical clade: Sporothrix brasiliensis, Sporothrix schenckii, Sporothrix globosa, and Sporothrix luriei. Zoonotic transmission by infected cats is particularly relevant in Brazil, with recorded outbreaks primarily in the country's Southeast region. In recent decades, this mode of transmission has been observed to expand beyond Brazilian borders. Current sporotrichosis treatment faces challenges in efficacy and implementation, justifying the search for new management strategies, such as drug repurposing and the use of natural compounds. Proton pump inhibitors (PPIs), such as omeprazole and rabeprazole, widely used for gastrointestinal disorders, have demonstrated proven inhibitory activity against pathogenic fungi. Chitosan, a natural, low-toxicity, and biodegradable product, has been used in the formulation of microparticles to encapsulate antifungal molecules, protecting them from degradation and increasing their bioavailability. In this context, this study evaluated the antifungal potential of chitosan microparticles loaded with omeprazole and rabeprazole (MQOMP and MQRBP, respectively) against 12 strains of the Sporothrix spp. clinical clade. The fungi were cultured in filamentous form, and planktonic cells were subjected to antifungal susceptibility testing in 96-well plates using the broth microdilution method, following CLSI protocols. The plates were incubated at 35°C for 72 hours, and after the growth period, a visual reading was performed to determine the minimum inhibitory concentration (MIC) capable of inhibiting 50%, 80%, and 100% of fungal growth. All tested strains were susceptible to omeprazole and rabeprazole encapsulated in chitosan microparticles. The results obtained in the MQOMP and MQRBP assays ranged from 0.5 to 1 μg/mL and 0.25 to 1 μg/mL for 50% inhibition, 1 to 2 μg/mL and 0.5 to 1 μg/mL for 80% inhibition, and 2 to 4 μg/mL and 0.5 to 2 μg/mL for 100% fungal growth inhibition, respectively. Comparison with literature data indicates that chitosan encapsulation enhanced the antifungal activity of PPIs, showing a significant reduction in MIC against Sporothrix spp. This study supports promising new therapeutic approaches for sporotrichosis control and is pioneering in investigating the encapsulation of PPIs in chitosan to enhance antifungal action.