Comparative study of lipidic and polymeric nanoparticles encapsulating benznidazole in an acute mice model of Chagas disease.

Chagas disease is a neglected infectious disease endemic to Latin America. Only two approved medications are available, benznidazole (BNZ) and nifurtimox, and both have suboptimal efficacy in the chronic stage of the disease and severe side effects. To overcome these limitations, we previously described the development of a lipid nanoformulation of BNZ (NLC-BNZ). Here, we extended this work to polymeric nanoparticles (EU-BNZ) and evaluated both in vivo for pharmacokinetics (PK) and efficacy. At the highest concentration tested, nanoencapsulation notably reduced BNZ cytotoxicity in CHO cells (from 50% to 100% viability). No significant differences were found in the PK profiles between the formulations and the free drug, orally administered at doses equivalent to 30 mg/kg of BNZ. In the mouse model of acute T. cruzi infection, treatment with NLC-BNZ and EU-BNZ improved survival relative to controls (empty carriers or vehicle) but was not superior to free BNZ. Consistent with the in vitro observations, mice treated with NLC showed a higher survival percentage compared to their polymeric counterparts. This finding highlights lipidic nanoparticles not merely as carriers but as potential therapeutic agents. Our findings provide a promising starting point for the exploration of lipidic compounds with potential intrinsic antiparasitic properties.