da Silva Yngrid Batista, Bedogni Giselle, de Andrade Picanço Guaraciara, de Souza Jéssica Yonara, Nunes Waylla Silva, da Costa Tatiane Luiza, de Campos Geovana Batista, Vargas Michelena Lina, Salomon Claudio Javier, Vinaud Marina Clare
Laboratory of Host-Parasite Relationship Studies, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goias, Brazil.
Institute of Chemistry of Rosario (IQUIR-CONICET), Rosario, Argentina.
Pharm Dev Technol. 2024 Dec;29(10):1093-1100. doi: 10.1080/10837450.2024.2422936. Epub 2024 Nov 9.
This work aimed to develop fenbendazole nanocrystals to evaluate their effects on the energetic metabolism of cysticerci, following an intracranial inoculation in mice.
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 study was performed in infected animals treated with nanoformulated fenbendazole and raw drug and their metabolic impact was quantified by analyzing specific metabolites.
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 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.
These findings suggest that nanoformulated fenbendazole may be considered a valuable approach for an effective treatment of neurocysticercosis.
本研究旨在制备芬苯达唑纳米晶体,以评估其对小鼠颅内接种猪囊尾蚴能量代谢的影响。
采用反溶剂法,以泊洛沙姆188和407作为稳定剂,对芬苯达唑进行纳米制剂化。纳米混悬液在无冷冻保护剂的情况下冻干,对纳米晶体的粒径、zeta电位和溶解性能进行表征。在感染动物中开展研究,分别用纳米制剂化芬苯达唑和原料药进行治疗,并通过分析特定代谢物对其代谢影响进行定量。
通过纳米沉淀法获得芬苯达唑样品,产率>80%。冻干样品的平均粒径在372nm至1600nm之间。与原料药相比,纳米体系向溶液中释放了更多的药物。研究表明,芬苯达唑治疗组诱导了糖异生、三羧酸循环部分受阻以及蛋白质分解代谢增加。可见,纳米制剂对这些参数的影响比原料药更大,导致寄生虫代谢发生显著改变,进而可能影响感染的总体进程和治疗结果。
这些发现表明,纳米制剂化芬苯达唑可能是有效治疗神经囊尾蚴病的一种有价值的方法。