Benznidazole self-emulsifying delivery system: A novel alternative dosage form for Chagas disease treatment

• Published in: European journal of pharmaceutical sciences 2020-03, Vol.145, p.105234-105234, Article 105234
• Main Authors: Mazzeti, Ana Lia, Oliveira, Liliam Teixeira, Gonçalves, Karolina R., Schaun, Géssica C., Mosqueira, Vanessa Carla Furtado, Bahia, Maria Terezinha
• Format: Article
• Language: English
• Subjects: Benznidazole; Chagas disease; Cytotoxicity; Efficacy; Release kinetics; Self-emulsifying drug delivery system; Trypanosoma cruzi
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2020.105234

Benznidazole (BZ) tablets are a unique form of treatment available for treating Chagas disease. Development of a liquid formulation containing BZ easy to administer orally for the treatment of paediatric patients, particularly for newborns is urgently required, with the same efficacy, safety and suitable biopharmaceutical properties as BZ tablets. Self-emulsifying drug delivery systems (SEDDS) may improve bioavailability of drugs such as BZ, which have poor water solubility and low permeability. In this context, the aim of this work was to develop a liquid BZ-SEDDS formulation as an alternative to tablets and to evaluate its cytotoxicity in different host cell lines and its efficacy in experimental Trypanosoma cruzi infection in mice. The optimized SEDDS formulation (25 mg/ml of BZ) induced no cytotoxicity in H9c2, HepG2 and Caco2 cells in vitro at 25 μM level. BZ-SEDDS and free-BZ showed similar in vitro trypanocidal activity in H9c2 cells infected by T. cruzi Y strain, with IC50 values of 2.10 ± 0.41 μM and 1.29 ± 0.01 μM for BZ and BZ-SEDDS, respectively. A follow up of efficacy in an acute model of infected mice resulted in the same percentage of cure (57%) for both free-BZ and BZ-SEDDS- groups according to established parameters. Furthermore, no additional in vivo toxicity was observed in animals treated with BZ-SEDDS. Taken together, in vitro and in vivo data of BZ-SEDDS showed that the incorporation of BZ into SEDDS does not alter its potency, efficacy and safety. Thus, BZ-SEDDS can be a more practical and personalized orally administered liquid dosage form compared to suspension of crushed BZ-tablets to treat newborn and young children by emulsifying SEDDS in different aqueous liquids with advantage of dosing flexibility. [Display omitted]