NANOFORMULATIONS OF BENZNIDAZOLE IN THE TREATMENT OF CHRONIC MURINE INFECTION BY TRYPANOSOMA CRUZI NICARAGUA

MÓNICA ESTEVA; PRADO, NILDA; ARRÚA E.C.; BUA, JACQUELINE; FICHERA L.E.; RIAL MARCELA; NANA YESICA; SALOMON C.J

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS

We evaluated the effect of new Benznidazole nanoformulations (BNZ-nps) in mice with chronic infection by T. cruzi Nicaragua (TcN) with the aim of reduce the progression of cardiac pathology with low doses of administered drug and avoiding the adverse effects of BNZ evidenced in patients.In previous work, acute TcN-infected C3H/HeN mice treated with 30 doses of BNZ-nps at concentrations of 10, 25 or 50 mg/kg/day, survived a 100%. The specific antibody titers for T. cruzi were negative at 6 months post infection with 25 and 50 BNZ-nps. Parasitemia by PCR showed that 80% of the mice treated with BNZ-nps 25 mg/kg/day were negative for TcN and 50% with BNZ-nps 50 mg/kg/day. The hearts of the untreated infected mice showed multiple and extensive inflammatory foci that with BNZ-nps treatments are reversed.In this study, TcN-infected C57BL/6J mice were treated in the chronic phase of infection with 30 daily doses of BNZ-nps at concentrations of 25 or 50 mg/kg/day or 13 intermittent doses (1 dose each 7 days) of 50 or 75 mg/kg/day. The different treatments effectiveness was evaluated measuring parasitemia by qPCR, serology by ELISA, inflammation and fibrosis indexes by histopathology of hearts and electrical alterations by electrocardiograms.With all treatments: 100% of the qPCR were negative, inflammation and fibrosis significantly decreased as well as antibody titers specific for T. cruzi. In addition, electrocardiograms showed the normalization of the decrease of the heart rate and the PR interval. For this, we can choose the intermittent treatment of 50 mg/kg/day, because with a lower total dose of BNZ (650 mg/kg) we obtain similar results (without significant differences) that whit high doses of the daily treatment.BNZ-nps treatment may be effective in successfully treat Chagas´ disease in experimental models of acute and chronic T. cruzi infection by decreasing the amount of BNZ administered without loss the efficacy.Keywords: Nanoformulations, Benznidazole, Chagas´ disease, Trypanosoma cruzi