Drug repurposing for experimental neurocysticercosis: in vitro and in vivo evaluation of nanoformulated triclabendazole

Abstract

Current pharmacological treatment of neurocysticercosis relies primarily on albendazole; however, despite its efficacy, its clinical use is limited by treatment-associated inflammatory complications. In this context, drug repurposing combined with nanotechnology-based drug delivery systems represents a promising strategy to improve therapeutic outcomes. Thus, the potential repurposing of triclabendazole, the benzimidazole drug of choice for fascioliasis, was investigated by assessing the metabolic effects of its nanoformulation in an experimental model of neurocysticercosis. Triclabendazole nanoparticles stabilized with poly(vinylpyrrolidone) were prepared by spray drying and characterized in terms of production yield, particle size, zeta potential, polydispersity index, Fourier-transform infrared spectroscopy, X-ray diffraction, in vitro drug release, and hemocompatibility. The spray-drying process achieved production yields ranging from 75% to 81%. Particle size increased from approximately 100–220 nm before drying to 300–400 nm after redispersion of the dried powder. Physicochemical analyses demonstrated that triclabendazole was predominantly present in an amorphous state within the nanosystem. In vitro dissolution studies showed a marked enhancement in drug release compared with the raw drug, while hemolysis assays confirmed acceptable hemocompatibility. In vivo metabolomic evaluation of Taenia crassiceps cysticerci following treatment with the nanoformulation revealed significant alterations in metabolic pathways associated with energy production and parasite survival, indicating a profound disruption of parasite metabolism. To our knowledge, this is the first study demonstrating the potential of nanoformulated triclabendazole as a repurposed therapeutic strategy for neurocysticercosis while providing mechanistic evidence of its effects on parasite metabolism.