DEVELOPMENT AND EVALUATION OF POLYMERIC NANOPARTICLES CONTAINING AMPHOTERICIN B FOR ENHANCED SKIN PENETRATION USING AN EX VIVO PORCINE EAR MODEL.

Amphotericin B (AmB) is a broad-spectrum antifungal agent, widely used to treat fungal infections and neglected parasitic diseases, such as leishmaniasis. Despite its therapeutic efficacy, its clinical use is limited by low oral bioavailability, toxicity, and adverse effects associated with treatment. In this context, alternative drug delivery systems, such as polymeric nanoparticles (PNPs), are being investigated for their ability to protect the active ingredient, enable controlled release, and enhance bioavailability, thereby improving therapeutic efficacy and reducing toxicity. The objective for this work was to evaluate poly(lactic acid) (PLA) and polycaprolactone (PCL) polymeric nanoparticles loaded with amphotericin B, aiming for topical application and an analysis of their skin penetration capacity. PNPs were produced by nanoprecipitation and characterized using dynamic light scattering (to determine particle size), transmission electron microscopy (for morphological assessment), and Raman spectroscopy (to confirm drug incorporation). Formulation stability was investigated using static multiple light scattering (SMLS) analysis. Skin penetration capacity was evaluated using an ex vivo porcine ear model, tape stripping technique and histopathology. The results demonstrated the successful production of AmB-PNPs with characteristics suitable for topical application. PLA nanoparticles loaded with AmB were able to reach the viable epidermis, indicating greater skin penetration depth. In contrast, PCL nanoparticles loaded with the drug remained predominantly in the stratum corneum, the outermost layer of the skin. Stability studies indicated behavior consistent with the maintenance of the formulations' physicochemical properties throughout the evaluated period. In conclusion, the findings suggest that both formulations have potential for topical therapeutic application, although they exhibit distinct cutaneous distribution profiles. PLA nanoparticles demonstrated greater penetration capacity, whereas PCL nanoparticles favored superficial drug retention. Thus, amphotericin B-loaded PLA and PCL nanoparticulate systems represent promising alternatives for treating cutaneous fungal infections and leishmaniasis, potentially enhancing therapeutic efficacy and reducing adverse effects associated with conventional drug administration methods.