Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDSs) for senicapoc
Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDSs) for senicapoc
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DOI：
10.1016/j.ijpharm.2020.119180
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发表时间：
2020-04-30
影响因子：
5.8
通讯作者：
Preat, Veronique
中科院分区：
文献类型：
--
作者：
Buya, Aristote B.;Ucakar, Bernard;Preat, Veronique
Senicapoc（SEN）是一种有效的抗镰状病剂，但水溶性差，口服生物利用度低。为了提高SEN的溶解度和细胞渗透性，人们开发了自纳米乳化给药系统（SNEDDS）。选择表现出最高增溶能力的Capryol PGMC（R）作为油。研究了两种表面活性剂的自乳化能力，比较Cremophor-EL（R）和Tween（R）80。基于溶解度研究和三元相图，制备了三种液滴尺寸小于200 nm的优化纳米乳液。体外溶出研究表明SNEDDS的上级性能优于游离药物。在体外脂解过程中，SNEDDS中80%的SEN保持溶解。使用Caco-2细胞系进行的体外细胞毒性研究表明，1 mg/mL制剂具有安全性。与游离药物相比，SEN-SNEDDS穿过Caco-2单层的转运增强了115倍（p < 0.01）。根据这些结果，SNEDDS制剂可能是用于口服递送SEN的有前途的工具。
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 (R), which showed the highest solubilization capacity, was selected as the oil. The self-emulsification ability of two surfactants, viz., Cremophor-EL (R) and Tween (R) 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.