AOKI MARIA DEL PILAR
Congresos y reuniones científicas
Título:
BENZNIDAZOLE-LOADED MULTIPARTICULATE DRUG DELIVERY SYSTEMS IMPROVE EXPERIMENTAL CHAGAS DISEASE PHARMACOTHERAPY
Autor/es:
GARCÍA, MC; SANMARCO, LM; PONCE, NE; JIMENEZ KAIRUZ, A; AOKI, MP
Reunión:
Congreso; Reunión conjunta de Sociedades de Biociencias; 2017
Resumen:
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<0.001). At different schemes of therapies, both pure BZ or loaded
in the MDDS at 100 mg/kg, were able to override the parasitemia
in comparison to INT mice (p<0.001), and at 50 mg/kg the treatments allow reducing the parasitemia levels (p<0.05). Before immunosuppression, the percentage of ROS-producing circulating cells
was higher at 50 mg/kg (p<0.001) compared with BZ at 100 mg/kg,
which could be explained due to parasite persistence. BZ-loaded
MDDS treatments showed a significant reduction in heart damage
(p<0.05) compared to the reference treatment. Thus, BZ-loaded
MDDS seems to be safer than pure BZ at 100 mg/kg preserving the
efficacy for the treatment of Chagas disease.
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<0.001). At different schemes of therapies, both pure BZ or loaded
in the MDDS at 100 mg/kg, were able to override the parasitemia
in comparison to INT mice (p<0.001), and at 50 mg/kg the treatments allow reducing the parasitemia levels (p<0.05). Before immunosuppression, the percentage of ROS-producing circulating cells
was higher at 50 mg/kg (p<0.001) compared with BZ at 100 mg/kg,
which could be explained due to parasite persistence. BZ-loaded
MDDS treatments showed a significant reduction in heart damage
(p<0.05) compared to the reference treatment. Thus, BZ-loaded
MDDS seems to be safer than pure BZ at 100 mg/kg preserving the
efficacy for the treatment of Chagas disease.
