Nanoformulated fenbendazole as an attractive approach for treating neurocysticercosis: in vitro and in vivo studies

Abstract

Purpose: This work aimed to develop fenbendazole nanocrystals to evaluate their effects on the energeticmetabolism of Taenia crassiceps cysticerci, following an intracranial inoculation in mice.Methods: Fenbendazole was nanoformulated by the antisolvent method using poloxamers 188 and 407as stabilizers. The nanosuspensions were lyophilized without cryoprotectants and the nanocrystals werecharacterized in terms of particle size, zeta potential, and dissolution performance. The in vivo study wasperformed in infected animals treated with nanoformulated fenbendazole and raw drug and their metabolicimpact was quantified by analyzing specific metabolites.Results: Fenbendazole samples were obtained by nanoprecipitation in > 80% yield. The average particlesize of the freeze-dried samples was between 372 nm and 1600 nm. The nanosystems released a greateramount of the drug into the solution, compared to the raw drug. The in vivo studies showed that thefenbendazole-treated groups induced gluconeogenesis, partial blockage of the TCA cycle, and increasedprotein catabolism. As seen, the nanoformulation presented a greater effect on these parameters thanthe raw drug leading to remarkable modifications in the metabolism of the parasite, which in turn caninfluence the overall course of the infection and treatment outcomes.Conclusion: These findings suggest that nanoformulated fenbendazole may be considered a valuableapproach for an effective treatment of neurocysticercosis.