Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials Group, Avenue Mounier 73, B1.73.12, 1200 Brussels, Belgium; University of Kinshasa, Faculty of Pharmaceutical Sciences, Pharmaceutics and Phytopharmaceutical Drug Development Research Group, BP 212 Kinshasa XI, Congo.
Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials Group, Avenue Mounier 73, B1.73.12, 1200 Brussels, Belgium.
Int J Pharm. 2020 Apr 30;580:119180. doi: 10.1016/j.ijpharm.2020.119180. Epub 2020 Mar 3.
Senicapoc (SEN), a potent antisickling agent, shows poor water solubility and poor oral bioavailability. To improve the solubility and cell permeation of SEN, self-nanoemulsifying drug delivery systems (SNEDDSs) were developed. Capryol PGMC®, which showed the highest solubilization capacity, was selected as the oil. The self-emulsification ability of two surfactants, viz., Cremophor-EL® and Tween® 80, was compared. Based on a solubility study and ternary phase diagrams, three optimized nanoemulsions with droplet sizes less than 200 nm were prepared. An in vitro dissolution study demonstrated the superior performance of the SNEDDS over the free drug. During in vitro lipolysis, 80% of SEN loaded in the SNEDDS remained solubilized. An in vitro cytotoxicity study using the Caco-2 cell line indicated the safety of the formulations at 1 mg/mL. The transport of SEN-SNEDDSs across Caco-2 monolayers was enhanced 115-fold (p < 0.01) compared to that of the free drug. According to these results, SNEDDS formulations could be promising tools for the oral delivery of SEN.
Senicapoc（SEN）是一种有效的抗镰状化药物，但其水溶性差，口服生物利用度低。为了提高 SEN 的溶解度和细胞通透性，开发了自微乳给药系统（SNEDDS）。Capryol PGMC®具有最高的增溶能力，被选为油相。比较了两种表面活性剂 Cremophor-EL®和 Tween® 80 的自乳化能力。基于溶解度研究和三元相图，制备了三种优化的纳米乳，其粒径均小于 200nm。体外溶出度研究表明 SNEDDS 优于游离药物。在体外脂肪酶水解实验中，80%负载于 SNEDDS 中的 SEN 仍保持溶解状态。使用 Caco-2 细胞系进行的体外细胞毒性研究表明，在 1mg/mL 时制剂是安全的。与游离药物相比，SEN-SNEDDS 穿过 Caco-2 单层的转运增加了 115 倍（p<0.01）。根据这些结果，SNEDDS 制剂可能是 SEN 口服递送的有前途的工具。
