Benznidazole-loaded multiparticulate drug delivery systems improve experimental Chagas disease pharmacotherapy

PONCE, NICOLÁS; GARCÍA, MÓNICA C; JIMENEZ KAIRUZ, ALVARO; EBERHARDT, NATALIA; AOKI, MARÍA P.; SANMARCO, LILIANA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Benznidazole (BZ) is the selected drug for Chagas disease treatment, showing a parasitological cure rate of 60-80% during the acute phase. High frequency of administration, long-term treatment, and several side effects are issues that negatively affect therapeutic success. We have developed BZ-loaded multiparticulate drug delivery systems (MDDS) that showed modified release of BZ. These pharmaceutical strategies would reduce side effects of BZ and/or allow reducing its frequency of administration. The present work aimed to evaluate the efficacy and safety of BZ-loaded MDDS compared to the reference treatment (BZ 100 mg/kg daily) in a murine model of Chagas disease. BALB/c mice were ip infected with 1000 Tulahuen trypomastigotes, and after 15 days post-infection (dpi) were orally treated with BZ-loaded MDDS or pure BZ at 50 and 100 mg/kg daily or intermittent (2 or 5 day intervals). In order to accurately assess efficacy, at 105 dpi mice were immunosuppressed with 4 doses of cyclophosphamide at 3 day intervals. Then, mice were sacrificed and parasitemia, parasite heart-load, relative weight of spleens, livers and hearts, and tissue injury biomarkers were analyzed. Treated animals presented a survival higher than 80% compared to mice infected and non-treated (INT) which showed a survival of 9% (p