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

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  • 1 Instituto Nacional de Parasitología Dr. Mario Fatala Chaben, ANLIS CG Malbrán, Ministerio de Salud, Buenos Aires, Argentina.
  • | 2 Instituto de Química Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIR-CONICET), Rosario, Argentina.
  • | 3 Area Técnica Farmacéutica, Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
  • | 4 Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.

The aim of this study was to evaluate the effectiveness of benznidazole nanoparticles (BNZ-nps) on trypomastigote forms and on intracellular infection in mammalian cells and primary cardiac myocyte cells. Its effectiveness was also evaluated on acute Trypanosoma cruzi Nicaragua mice infection. Trypomastigotes from culture were treated 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 percentage of amastigote inhibition. C3H/HeN mice with lethal acute infection were treated with 10, 25, and 50 mg/kg/day of BNZ-nps for 30 and 15 days to control the survival rate of animals. BNZ-nps having a mean particle size of 63.3 nm, a size distribution 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 mammalian cells. 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 showed a 70% survival rate. The results obtained demonstrate, for the first time, that benznidazole nanoparticles are a useful and attractive approach to treat Chagas disease in infected mice.

Author Notes

* Address correspondence to: Claudio J. Salomon, Instituto de Química Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIR-CONICET), Suipacha 531, 2000, Rosario, Argentina, E-mail: csalomon@fbioyf.unr.edu.ar or Laura E. Fichera, Instituto Nacional de Parasitología Dr. Mario Fatala Chaben, ANLIS CG Malbrán, Ministerio de Salud, Avenida Paseo Colón 568 Ciudad de Buenos Aires, Argentina, E-mail: lfichera@yahoo.com. † These authors contributed equally to this work.

Financial support: This work was partially supported by the Instituto Nacional de Parasitología, ANLIS CG Malbrán, CONICET (National Council Research, Argentina, PIP 483 and PIP 194), Focanlis 2011, National University of Rosario, Argentina, and ANPCYT (National Agency of Science and Technology, Argentina, PICT 1078). Eva C. Arrúa acknowledges ANPCYT for fellowship grant.

Authors' addresses: María L. Scalise, Marcela S. Rial, and Mónica I. Esteva, Instituto Nacional de Parasitología Dr. Mario Fatala Chaben, ANLIS CG Malbrán, Ministerio de Salud, Buenos Aires, Argentina, E-mails: scaliselujan@yahoo.com.ar, marcelarial2@hotmail.com, and miesteva@yahoo.com. Eva C. Arrúa, Instituto de Química Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIR-CONICET), Rosario, Argentina, E-mail: arruacarolina@gmail.com. Claudio J. Salomon, Instituto de Química Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIR-CONICET), Rosario, Argentina, and Área Técnica Farmacéutica, Departamento Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina, E-mails: csalomon@fbioyf.unr.edu.ar or salomon@iquir-conicet.gov.ar. Laura E. Fichera, Instituto Nacional de, Parasitología Dr. Mario Fatala Chaben ANLIS CG Malbrán, Ministerio de Salud, Buenos Aires, Argentina, and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina, E-mail: lfichera@yahoo.com.

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