Hydrophilic and hydrophobic polymeric benznidazole-loaded nanoparticles: Physicochemical properties and in vitro antitumor efficacy

Abstract

Benznidazole is a promising antitumor drug because it has the ability to induce the production of intracellular reactive oxygen species. In this study, poly(d,l-lactide-co-glycolide), a hydrophobic polymer, and Eudragit® E PO, a hydrophilic polymer, were used to prepare nanoparticles and evaluated for their abilities to improve drug antitumor efficacy. Nanoparticles were prepared using the emulsification-solvent evaporation method. Particle size, zeta potential, encapsulation efficiency, attenuated total reflectance Fourier transformation infrared spectroscopy, and in vitro drug release were assessed for all formulations. Formulations with Eudragit® E PO produced cationic (>+25 mV) nanoparticles, which were smaller (<160 nm) than those prepared with poly(d,l-lactide-co-glycolide) (<250 nm), which were negatively charged (−2 mV). Use of poly(d,l-lactide-co-glycolide) resulted in the highest encapsulation efficiency. However, the hydrogel characteristics of Eudragit® E PO resulted in the slowest drug release rate. Cytotoxicity assays using the human embryonic kidney cell line HEK 293, the human liver cancer cell line Hep G2, and the human colon cancer cell line HT-29 demonstrated that nanoparticle formulations with the two polymers improved the biological activity of benznidazole. However, cationic and hydrophilic nanoparticles induced greater cytotoxicity. This study provided useful information regarding preformulation of polymeric nanoparticles to improve drug uptake.