Choi Goeun, Piao Huiyan, Rejinold N Sanoj, Yu Seungjin, Kim Ki-Yeok, Jin Geun-Woo, Choy Jin-Ho
Intelligent Nanohybrid Materials Laboratory (INML), Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Korea.
College of Science and Technology, Dankook University, Cheonan 31116, Korea.
Pharmaceuticals (Basel). 2021 May 19;14(5):486. doi: 10.3390/ph14050486.
COVID-19 has been affecting millions of individuals worldwide and, thus far, there is no accurate therapeutic strategy. This critical situation necessitates novel formulations for already existing, FDA approved, but poorly absorbable drug candidates, such as niclosamide (NIC), which is of great relevance. In this context, we have rationally designed NIC-loaded hydrotalcite composite nanohybrids, which were further coated with Tween 60 or hydroxypropyl methyl cellulose (HPMC), and characterized them in vitro. The optimized nanohybrids showed particle sizes <300 nm and were orally administrated to rats to determine whether they could retain an optimum plasma therapeutic concentration of NIC that would be effective for treating COVID-19. The pharmacokinetic (PK) results clearly indicated that hydrotalcite-based NIC formulations could be highly potential options for treating the ongoing pandemic and we are on our way to understanding the in vivo anti-viral efficacy sooner. It is worth mentioning that hydrotalcite-NIC nanohybrids maintained a therapeutic NIC level, even above the required IC value, after just a single administration in 8-12 h. In conclusion, we were very successfully able to develop a NIC oral formulation by immobilizing with hydrotalcite nanoparticles, which were further coated with Tween 60 or HPMC, in order to enhance their emulsification in the gastrointestinal tract.
新型冠状病毒肺炎已在全球影响了数百万人，到目前为止，尚无准确的治疗策略。这种危急情况需要为已有的、经美国食品药品监督管理局批准但吸收性差的候选药物设计新的制剂，如氯硝柳胺（NIC），这具有重大意义。在此背景下，我们合理设计了负载氯硝柳胺的水滑石复合纳米杂化物，并用吐温60或羟丙基甲基纤维素（HPMC）对其进行进一步包衣，并对其进行了体外表征。优化后的纳米杂化物粒径小于300nm，并经口服给予大鼠，以确定它们是否能保持对治疗新型冠状病毒肺炎有效的氯硝柳胺最佳血浆治疗浓度。药代动力学（PK）结果清楚地表明，基于水滑石的氯硝柳胺制剂可能是治疗当前大流行的极具潜力的选择，我们正在尽快了解其体内抗病毒疗效。值得一提的是，水滑石-氯硝柳胺纳米杂化物在单次给药8至12小时后，就能维持治疗性氯硝柳胺水平，甚至高于所需的IC值。总之，我们通过用水滑石纳米颗粒固定，进一步用吐温60或羟丙基甲基纤维素包衣，非常成功地开发了一种氯硝柳胺口服制剂，以增强其在胃肠道中的乳化作用。
