POLYMERIC NANOPARTICLES FOR AMPHOTERICIN B DELIVERY: TOXICOLOGICAL ASSESSMENT USING ZEBRAFISH EMBRYOS

 Amphotericin B (AmB) is a widely used antifungal drug, also employed in the treatment of neglected tropical diseases such as leishmaniasis. However, its clinical application is hindered by low oral bioavailability and high toxicity, prompting the development of alternative drug delivery systems. Among these, polymeric nanoparticles (PNPs) have attracted attention due to their potential to provide controlled release, enhanced permeability, and reduced adverse effects. Despite these benefits, concerns regarding the toxicity of nanomaterials persist, highlighting the need for robust biological assessment models. In this study, PNPs based on poly(lactic acid) (PLA) and polycaprolactone (PCL) containing AmB were prepared by nanoprecipitation and characterized using dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), scanning transmission electron microscopy (STEM), and atomic force microscopy (AFM). The in vivo toxicity of the formulations was evaluated using zebrafish (Danio rerio) embryos, a well-established model due to its genetic similarity to humans and standardized embryonic development assays. The results showed that nanoencapsulation increased AmB toxicity in zebrafish compared to the free drug, likely due to enhanced drug penetration observed by fluorescence microscopy. However, PLA and PCL polymers alone were not associated with significant toxicity, confirming their biocompatibility. The improved permeability conferred by nanoencapsulation suggests that lower doses of AmB may be required to achieve therapeutic efficacy while reducing toxicity. In conclusion, nanoencapsulation of AmB enhances drug penetration and therapeutic potential, but careful dose adjustment is necessary to minimize toxicity. The zebrafish model proved to be an effective platform for assessing the safety and efficacy of nanostructured drug delivery systems.