In vitro studies and preclinical evaluation of benznidazole microparticles in the acute Trypanosoma cruzi murine model

RIAL M.; SEREMETA K.; ESTEVA M.; BUA J.; SALOMON C; FICHERA L.

PARASITOLOGY

CAMBRIDGE UNIV PRESS

Lugar: Cambridge; Año: 2020 vol. 148

0031-1820

Chagas disease is a serious parasitic infection caused by Trypanosoma cruzi. Unfortunately,the current chemotherapeutic tools are not enough to combat the infection. The aim ofthis study was to evaluate the trypanocidal activity of benznidazole-loaded microparticles duringthe acute phase of Chagas infection in an experimental murine model. Microparticles wereprepared by spray-drying using copolymers derived from esters of acrylic and methacrylicacids as carriers. Dissolution efficiency of the formulations was up to 3.80-fold greater thanthat of raw benznidazole. Stability assay showed no significant difference (P > 0.05) in theloading capacity of microparticles for 3 years. Cell cultures showed no visible morphologicalchanges or destabilization of the cell membrane nor haemolysis was observed in defibrinatedhuman blood after microparticles treatment. Mice with acute lethal infection survived 100%after 30 days of treatment with benznidazole microparticles (50 mg kg−1 day−1).Furthermore, no detectable parasite load measured by quantitative polymerase chain reactionand lower levels of T. cruzi-specific antibodies by enzyme-linked immunosorbent assay werefound in those mice. A significant decrease in the inflammation of heart tissue after treatmentwith these microparticles was observed, in comparison with the inflammatory damageobserved in both infected mice treated with raw benznidazole and untreated infected mice.Therefore, these polymeric formulations are an attractive approach to treat Chagas disease.