A new oral self-emulsifying drug delivery system improves the antileishmania efficacy of fexinidazole in vivo

The aim of this study was to develop, characterize and evaluate the in vivo oral efficacy of self-emulsifying drug delivery systems (SEDDS) containing fexinidazole (FEX) in the experimental treatment of visceral leishmaniasis (VL). The developed FEX-SEDDS formulation presented as a clear, yellowish liquid, with absence of precipitate. The droplet size, polydispersion index and zeta potential after dilution in water (1:200) was of 91 ± 3 nm, 0.242 ± 0.005 and −16.7 ± 0.2, respectively. In the simulated gastric and intestinal media, the FEX-SEDDS had a size of 97 ± 1 and 106 ± 9 nm, respectively.

Highlights

• Fexinidazole-loaded self-emulsifying drug delivery systems (FEX-SEDDS) were developed.

• SEDDS formed nanoemulsions with small and homogeneous globules after dilution.

• No evidence of injury to the intestinal mucosa induced by oral FEX-SEDDS.

• Oral SEDDS reduced the parasite burden in Leishmania infantum-infected animals.

• They can be a promising oral alternative for the treatment of leishmania visceral.

The FEX retention in droplet after SEDDS dilution in simulated gastrointestinal media was almost 100 %. Antileishmanial efficacy studies showed that FEX-SEDDS was the only treatment able to significantly (p < 0.05) reduce the parasite burden in the liver and spleen of animals experimentally infected with Leishmania infantum. Our intestinal permeability data suggest that FEX-SEDDS showed no evidence of injury to the intestinal mucosa. These findings suggest that FEX-SEDDS can be a promising oral alternative for the treatment of VL caused by L. infantum.

Danielle Sóter do Nascimento Damasio, Patrícia Andrade Antunes, Eduardo Burgarelli Lages, Eliane de Morais-Teixeira, Kátia Duarte Vital, Valbert Nascimento Cardoso, Simone Odılia Antunes Fernandes, Marta Gontijo Aguiar, Lucas Antônio Miranda Ferreira, A new oral self-emulsifying drug delivery system improves the antileishmania efficacy of fexinidazole in vivo, International Journal of Pharmaceutics, Volume 631, 2023, 122505, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2022.122505.