info:eu-repo/semantics/article
In vitro studies and preclinical evaluation of benznidazole microparticles in the acute Trypanosoma cruzi murine model
Fecha
2020-12Registro en:
Rial, Marcela Silvina; Seremeta, Katia Pamela; Esteva, Mónica Inés; Bua, Jacqueline Elena; Salomon, Claudio Javier; et al.; In vitro studies and preclinical evaluation of benznidazole microparticles in the acute Trypanosoma cruzi murine model; Cambridge University Press; Parasitology; 148; 5; 12-2020; 566-575
0031-1820
1469-8161
CONICET Digital
CONICET
Autor
Rial, Marcela Silvina
Seremeta, Katia Pamela
Esteva, Mónica Inés
Bua, Jacqueline Elena
Salomon, Claudio Javier
Fichera, Laura Edith
Resumen
Chagas disease is a serious parasitic infection caused by Trypanosoma cruzi. Unfortunately, the current chaemotherapeutic tools are not enough to combat the infection. The aim of this study was to evaluate the trypanocidal activity of benznidazole-loaded microparticles during acute phase of Chagas infection in an experimental murine model. Microparticles were prepared by spray-drying using copolymers derived from esters of acrylic and methacrylic acids as carriers. Dissolution efficiency of the formulations was up to 3.80-fold greater than that of raw benznidazole. Stability assay showed no significant difference (p>0.05) in loading capacity of microparticles for three years. Cell cultures showed no visible morphological changes or destabilization of the cell membrane nor haemolysis was observed in defibrinated human blood after microparticles treatment. Mice with acute lethal infection survived 100% after 30-days treatment with benznidazole microparticles (50 mg/kg/day). Furthermore, no detectable parasite load measured by quantitative polymerase chain reaction and lower levels of T. cruzi-specific antibodies by enzyme-linked immunosorbent assay were found in those mice. A significant decrease in inflammation of heart tissue after treatment with these microparticles was observed, in comparison with the inflammatory damage observed in both infected mice treated with raw benznidazole and untreated infected mice. Therefore, these polymeric formulations are an attractive approach to treat Chagas disease.