Promising Efficacy of Benznidazole Nanoparticles in acute Trypanosoma cruzi Murine Model: In-Vitro and In-Vivo Studies

SCALISE MARÌA; ARRUA EVA; RIAL MARCELA; ESTEVA MONICA; SALOMON CLAUDIO; FICHERA LAURA

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE

AMER SOC TROP MED & HYGIENE

Lugar: Stanford; Año: 2016 vol. 95 p. 388 - 393

0002-9637

The aim of this study was to evaluate the effectiveness of benznidazole nanoparticles (BNZ-nps) ontrypomastigote forms and on intracellular infection in mammalian cells and primary cardiac myocyte cells. Its effectivenesswas also evaluated on acute Trypanosoma cruzi Nicaragua mice infection. Trypomastigotes from culture weretreated with different concentrations of BNZ-nps to determine the drug concentration that lyses 50% of trypomastigotes(LC50). Infected mammalian cells were incubated with different concentrations of BNZ-nps to determine the percentageof amastigote inhibition. C3H/HeN mice with lethal acute infection were treated with 10, 25, and 50 mg/kg/day of BNZnpsfor 30 and 15 days to control the survival rate of animals. BNZ-nps having a mean particle size of 63.3 nm, a sizedistribution of 3.35, and a zeta potential of −18.30 were successfully prepared using poloxamer 188 as a stabilizer.BNZ-nps 25 and 50 μg/mL showed no significant differences in the percentage of inhibition of infected mammaliancells. Infected mice treated with BNZ-nps (50, 25, and 10 mg/kg/day) for 30 days and with BNZ-nps (50 and 25 mg/kg/day)for 15 days presented a 100% survival, whereas the animals treated with 10 mg/kg/day for 15 days of BNZ-nps showeda 70% survival rate. The results obtained demonstrate, for the first time, that benznidazole nanoparticles are a usefuland attractive approach to treat Chagas disease in infected mice.