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 energetic metabolism of Taenia crassiceps cysticerci, following an intracranial inoculation in mice.

Methods: Fenbendazole was nanoformulated by the antisolvent method using poloxamers 188 and 407 as stabilizers. The nanosuspensions were lyophilized without cryoprotectants and the nanocrystals were characterized in terms of particle size, zeta potential, and dissolution performance. The in vivo study was performed in infected animals treated with nanoformulated fenbendazole and raw drug and their metabolic impact was quantified by analyzing specific metabolites.

Results: Fenbendazole samples were obtained by nanoprecipitation in > 80% yield. The average particle size of the freeze-dried samples was between 372 nm and 1600 nm. The nanosystems released a greater amount of the drug into the solution, compared to the raw drug. The in vivo studies showed that the fenbendazole-treated groups induced gluconeogenesis, partial blockage of the TCA cycle, and increased protein catabolism. As seen, the nanoformulation presented a greater effect on these parameters than the raw drug leading to remarkable modifications in the metabolism of the parasite, which in turn can influence the overall course of the infection and treatment outcomes.

Conclusion: These findings suggest that nanoformulated fenbendazole may be considered a valuable approach for an effective treatment of neurocysticercosis.