Page 343 - Resúmen - XXV Congreso Latinoamericano de Parasitología - FLAP

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New formulation of benznidazole: a novel alternative for Chagas disease

treatment

Mazzeti, Ana Lia ; Ribeiro Gonçalves, Karolina ; Teixeira Oliveira, Líliam ; Machado
1
2
2
Coelho, George ; Soeiro, Maria de Nazaré ; Furtado Mosqueira, Vanessa ; Bahia, Maria
1
3
4
Terezinha
3
1 Instituto Oswaldo Cruz, Fundação Oswaldo Cruz; Universidade Federal de Ouro Preto; Escola de
3
2
Medicina, Universidade Federal de Ouro Preto; Escola de Farmácia, Universidade Federal de Ouro Preto
4

Introduction: Benznidazole (BZ) is the drug widely used for treatment of Chagas disease, although it
shows variable and limited efficacy and several adverse effects. Development of new liquid dosage form
containing BZ could improve treatment efficacy and particularly to facilitate dose adjustment and
administration in paediatric patients. Self-emulsifying drug delivery systems (SEDDS) improve
bioavailability of poorly water soluble and/or low permeable drugs, as BZ. Aim: The aim of this work was
to develop a BZ-SEDDS formulation and evaluate its toxicity and its efficacy in Trypanossoma
cruzi experimental models in vitro and in vivo. Methods: BZ-SEDDS was prepared and characterized.
Initially, in vitro toxicity was evaluated using H9c2, HepG2 and Caco2 cells and anti- T. cruzi activity using
H9c2 cells infected by Y strain. In vivo assay using Swiss mice was performed to assess toxicity and
efficacy. Results: The optimized formulation (25 mg/ml of BZ) was stable and and suitable for
administration. BZ-SEDDS induced no cytotoxicity in H9c2, HepG2 and Caco2 cells in vitro at 25 μM level.
BZ-SEDDS and BZ showed similar in vitro trypanocidal activity, with IC50 equal 2.10 ± 0.41 μM and 1.29 ±
0.01 μM for BZ and BZ-SEDDS, respectively. A follow up of cure in acute model of infected mice resulted
in 57% (4 of 7) of cure for both BZ- and BZ-SEDDS groups according to established parameters of cure.
Furthermore, no additional in vivo toxicity was observed in animals treated with BZ-SEDDS according to
liver enzyme levels detected in animal serum. Conclusion: Taken together, in vitro and in vivo efficacy and
toxicity data of BZ-SEDDS showed that the incorporation of BZ into SEDDS does not alter its potency and
safety. Thus, BZ-SEDDS may be a safe and adjustable alternative oral dosage form for treatment of
paediatric patients with Chagas disease.

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