In the present study, a water insoluble drug named silybin was encapsulated into self-nanoemulsifying drug delivery system (SNEDDS) following the preparation of silybin-phospholipid complex (SB-PC), then several methods were carried out to characterize SB-PC-SNEDDS and elucidate its mechanisms to improve the oral absorption of SB. Using a dynamic in vitro digestion model, the lipolysis of SB-PC-SNEDDS was proved to be mainly related with the property of its lipid excipients. SB-PC-SNEDDS could significantly enhance the transport of SB across Caco-2 cells, which may partly attribute to the increased cell membrane fluidity and the loss of tight junction according to the analysis results of fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and tight junction protein (ZO-1). The result of in situ perfusion showed the intestinal absorption of SB from high to low was SB-PC-SNEDDS, SB-PC, and SB. The extent of lymphatic transport of SB-PC and SB-PC-SNEDDS via the mesenteric duct was 12.2 and 22.7 folds of that of SB, respectively. In the lymph duct cannulated rats, the relative bioavailability (Fr) of SB-PC and SB-PC-SEDDS compared to SB was 1265.9% and 1802.5%, respectively. All the above results provided mechanistic support for oral absorption improvement of water insoluble drugs by the combination of PC and SNEDDS.

中文翻译：

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磷脂复合物和SNEDDS组合可改善不溶性药物的口服吸收机制。

在本研究中，制备了水飞蓟宾-磷脂复合物（SB-PC）后，将一种水不溶性药物水飞蓟宾封装在自纳米乳化药物递送系统（SNEDDS）中，然后通过多种方法对其进行了表征。并阐明其改善SB口服吸收的机制。使用动态体外消化模型，证明SB-PC-SNEDDS的脂解作用主要与其脂质赋形剂的性质有关。根据1,6-diphenyl-1荧光各向异性的分析结果，SB-PC-SNEDDS可以显着增强SB跨Caco-2细胞的转运，这可能部分归因于细胞膜流动性的增加和紧密连接的丧失。 ，3,5-己三烯（DPH）和紧密连接蛋白（ZO-1）。原位灌注的结果显示，SB从高到低的肠道吸收为SB-PC-SNEDDS，SB-PC和SB。SB-PC和SB-PC-SNEDDS经由肠系膜导管的淋巴运输程度分别是SB的12.2倍和22.7倍。在淋巴管插管的大鼠中，SB-PC和SB-PC-SEDDS与SB的相对生物利用度（Fr）分别为1265.9％和1802.5％。以上所有结果为PC和SNEDDS的结合为改善水不溶性药物的口服吸收提供了机械支持。SB-PC和SB-PC-SEDDS与SB的相对生物利用度（Fr）分别为1265.9％和1802.5％。以上所有结果为PC和SNEDDS的结合为改善水不溶性药物的口服吸收提供了机械支持。SB-PC和SB-PC-SEDDS与SB的相对生物利用度（Fr）分别为1265.9％和1802.5％。以上所有结果为PC和SNEDDS的结合为改善水不溶性药物的口服吸收提供了机械支持。