Development of Polymeric Microneedles with Variable Lengths for Delivery of Ebselen in Sporotrichosis

Sporotrichosis is a subcutaneous mycosis of public health relevance due to the increased zoonotic transmission associated with felines. Ebselen (EB), a poorly water-soluble organic selenium compound, reacts with thiol groups of redox proteins, increases oxidative stress, and causes fungal death. Microneedles (MN) create microchannels in the skin, disrupting the stratum corneum and allowing the release and diffusion of the drug into deeper layers, potentially reaching blood capillaries. Sporotrichosis is typically treated with intravenous or oral therapies. Thus, this study developed polymeric MN for EB delivery, improving drug incorporation and dispersion while providing a minimally invasive topical alternative. A spectrophotometric method for EB analysis was validated. The molds (long and short microneedles) proved to be transparent, flexible, and easy to remove from the MN. The best formulations (F02, F09, F16, and F17) were selected. EB solubility was 0.15%. In light microscopy and scanning electron microscopy (SEM), both MN types presented well-defined and intact structures. In the compression test, the best formulation (F17) was selected in both molds. In vitro evaluation of the EB release profile from F17 showed that the long mold formulation released the drug faster than the short mold one. In vitro analysis of antifungal activity showed that the formulation containing EB induced the formation of an inhibitory halo, demonstrating antifungal activity against the fungus Sporothrix brasiliensis. Thus, the current results suggest that the MN containing EB is a promising system. Additional biological studies are required to fully assess their safety and performance in the context of sporotrichosis.