Ding Charles, Ding Yili, Xu Zhe, Wang Peini, Xu Shufeng
College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou, China.
Keck School of Medicine of USC, Los Angeles, CA, United States.
Front Vet Sci. 2025 Aug 7;12:1611154. doi: 10.3389/fvets.2025.1611154. eCollection 2025.
Mebendazole, approved by the Food and Drug Administration (FDA) in 1974 to expel intestinal parasite infections, was found to exhibit multiple anti-cancer activities. However, due to its poor water solubility (0.33 ± 0.02 μg/mL), its clinical applications were greatly limited. Scientists at Wenzhou-Kean University have developed a formulation that could increase its water solubility as much as 18,333 times to reach 6.05 mg/mL as the best result to date. Through the complexation with HP-beta-cyclodextrin, 80% of mebendazole in the complex was released in 5 min, and only 20% of mebendazole was released under the same conditions for the pure drug, in a pharmacokinetic study conducted on dogs with a dose of 5 mg/kg. The of mebendazole was increased from 8.96 ± 0.15 μg/mL to 17.34 ± 2.02 μg/mL. of mebendazole was shortened from 12.00 ± 0.50 h to 10 ± 0.50 h. The half lift time was prolonged from 5.81 ± 0.36 h to 10.01 ± 2.07 h; the was increased from 151.32 ± 5.92 μg·h/mL to 289.02 ± 15.83 μg·h/mL; and the bioavailability was improved by 91%, indicating that this complex can be pushed to the next step as an anti-tumor agent for its clinic practice.
甲苯咪唑于1974年被美国食品药品监督管理局（FDA）批准用于驱除肠道寄生虫感染，后来发现它具有多种抗癌活性。然而，由于其水溶性较差（0.33±0.02μg/mL），其临床应用受到极大限制。温州肯恩大学的科学家们开发了一种制剂，可将其水溶性提高多达18333倍，达到6.05mg/mL，这是迄今为止的最佳结果。在对剂量为5mg/kg的犬进行的药代动力学研究中，通过与HP-β-环糊精络合，络合物中80%的甲苯咪唑在5分钟内释放，而在相同条件下纯药物仅释放20%的甲苯咪唑。甲苯咪唑的血药浓度从8.96±0.15μg/mL增加到17.34±2.02μg/mL。甲苯咪唑的达峰时间从12.00±0.50小时缩短至10±0.50小时。半衰期从5.81±0.36小时延长至10.01±2.07小时；药时曲线下面积从151.32±5.92μg·h/mL增加到289.02±15.83μg·h/mL；生物利用度提高了91%，表明这种络合物作为一种抗肿瘤药物可推进到临床实践的下一步。
