Higher oral efficacy of ravuconazole in self-nanoemulsifying systems in shorter treatment in experimental chagas disease.
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Date
2021
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Abstract
We investigated the in vitro activity and selectivity, and in vivo efficacy of ravuconazole (RAV) in self-
nanoemulsifying delivery system (SNEDDS) against Trypanosoma cruzi. Novel formulations of this poorly solu-
ble C14-α-demethylase inhibitor may improve its efficacy in the experimental treatment. In vitro activity was
determined in infected cardiomyocytes and efficacy in vivo evaluated in terms of parasitological cure induced in
Y and Colombian strains of T. cruzi-infected mice. In vitro RAV-SNEDDS exhibited significantly higher potency of
1.9-fold at the IC50 level and 2-fold at IC90 level than free-RAV. No difference in activity with Colombian strain
was observed in vitro. Oral treatment with a daily dose of 20 mg/kg for 30 days resulted in 70% of cure for RAV-
SNEDDS versus 40% for free-RAV and 50% for 100 mg/kg benznidazole in acute infection (T. cruzi Y strain).
Long-term treatment efficacy (40 days) was able to cure 100% of Y strain-infected animals with both RAV
preparations. Longer treatment time was also efficient to increase the cure rate with benznidazole (Y and
Colombian strains). RAV-SNEDDS shows greater efficacy in a shorter time treatment regimen, it is safe and could
be a promising formulation to be evaluated in other pre-clinical models to treat T. cruzi and fungi infections.
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Keywords
Y strain, Trypanosoma cruzi, Ravuconazole, Self-nanoemulsifying drug delivery system, Efficacy
Citation
SPÓSITO, P. A. et al. Higher oral efficacy of ravuconazole in self-nanoemulsifying systems in shorter treatment in experimental chagas disease. Experimental Parasitology, v. 228, artigo 108142, 2021. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0014489421000795?via%3Dihub>. Acesso em: 11 out. 2022.