Higher oral efficacy of ravuconazole in self-nanoemulsifying systems in shorter treatment in experimental chagas disease

• Published in: Experimental parasitology Vol. 228; p. 108142
• Main Authors: Spósito, Pollyanna Álvaro, Mazzeti, Ana Lia, de Castro, Kelly Christyne Miranda Pereira, Mendes, Priscila Fagundes, Urbina, Julio A., Bahia, Maria Terezinha, Mosqueira, Vanessa Carla Furtado
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2021
• Subjects: Colombian strain; Efficacy; Ravuconazole; Self-nanoemulsifying drug delivery system; Toxicity; Trypanosoma cruzi; Y strain; Self-nanoemulsifying drug delivery system; Toxicity; Ravuconazole; Efficacy; Y strain; Trypanosoma cruzi; Colombian strain
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2021.108142

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 soluble 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. [Display omitted] •Self-nanoemulsifying delivery system improves the efficacy of ravuconazole.•SNEDDS incorporation increase ravuconazole potency in vitro in cardiomyoblasts infected with T. cruzi.•SNEDDS increased the RAV efficacy in 30 days' treatment of mice infected with the Y strain.•40 days' treatment increased the efficacy of RAV and BZ in mice infected by Y or Colombian strains.