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

Published online by Cambridge University Press:  10 December 2020

Marcela S. Rial ,
Katia P. Seremeta ,
Mónica I. Esteva ,
Jacqueline Búa ,
Claudio J. Salomon  and
Laura E. Fichera Open the ORCID record for Laura E. Fichera [Opens in a new window]
Marcela S. Rial
Affiliation:
Instituto Nacional de Parasitología Dr M. Fatala Chaben, ANLIS CG Malbrán, Ministerio de Salud, Av. Paseo Colón 568, Ciudad de Buenos Aires, Argentina
Katia P. Seremeta
Affiliation:
Departamento de Ciencias Básicas y Aplicadas, Universidad Nacional del Chaco Austral, Cte. Fernández 755, 3700, Pcia. Roque Sáenz Peña, Chaco, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Mónica I. Esteva
Affiliation:
Instituto Nacional de Parasitología Dr M. Fatala Chaben, ANLIS CG Malbrán, Ministerio de Salud, Av. Paseo Colón 568, Ciudad de Buenos Aires, Argentina
Jacqueline Búa
Affiliation:
Instituto Nacional de Parasitología Dr M. Fatala Chaben, ANLIS CG Malbrán, Ministerio de Salud, Av. Paseo Colón 568, Ciudad de Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Claudio J. Salomon*
Affiliation:
Instituto de Química Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIR-CONICET), Suipacha 531, 2000, Rosario, Argentina Área Técnica Farmacéutica, Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina
Laura E. Fichera*
Affiliation:
Instituto Nacional de Parasitología Dr M. Fatala Chaben, ANLIS CG Malbrán, Ministerio de Salud, Av. Paseo Colón 568, Ciudad de Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
*
Author for correspondence: Laura E. Fichera, E-mail: lfichera@yahoo.com; Claudio J. Salomon, E-mail: csalomon@fbioyf.unr.edu.ar
Author for correspondence: Laura E. Fichera, E-mail: lfichera@yahoo.com; Claudio J. Salomon, E-mail: csalomon@fbioyf.unr.edu.ar
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Abstract

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 of this study was to evaluate the trypanocidal activity of benznidazole-loaded microparticles during the 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 the loading capacity of microparticles for 3 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 of treatment with benznidazole microparticles (50 mg kg−1 day−1). 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 the 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.

Keywords

BenznidazoleChagas diseaseEudragit®experimental infectionmicroparticlesspray-drying
Type
Research Article
Information
Parasitology , Volume 148 , Issue 5 , April 2021 , pp. 566 - 575
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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