Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai 201203, China.
Int J Pharm. 2013 Mar 10;445(1-2):141-7. doi: 10.1016/j.ijpharm.2013.01.070. Epub 2013 Feb 8.
The purpose of this study was to examine whether Vitamin E-TPGS had a function in promoting the secretion of chylomicrons in enterocytes. Therefore, we simulated the human intestinal epithelial cells by Caco-2 cell model to study the effect of Vitamin E-TPGS on the chylomicron secretion in vitro. Meanwhile, chylomicron flow blocking rat model and mesenteric lymph cannulated rat model were used for the studies in vivo to evaluate the effect and probucol was chosen as the model drug. The results of cell experiments indicated that Vitamin E-TPGS at low concentration had a strong enhancement on the secretion of chylomicrons. The results of animal experiments indicated that Vitamin E-TPGS could significantly enhance the lymphatic transport of probucol by the same role consistently with the results obtained from cell experiments. However, the role would reach the plateau and saturate after a concentration dependent increase. These studies first demonstrate the function of Vitamin E-TPGS in the intestinal lymphatic transport of lipophilic drugs, which can significantly promote the secretion of chylomicrons by the intestinal epithelial cells.
本研究旨在探讨维生素 E-TPGS 是否具有促进肠上皮细胞乳糜微粒分泌的功能。因此,我们通过 Caco-2 细胞模型模拟人体肠道上皮细胞,研究维生素 E-TPGS 对乳糜微粒体外分泌的影响。同时,利用乳糜微粒阻断大鼠模型和肠系膜淋巴插管大鼠模型进行体内研究,以评估其效果,并选择普罗布考作为模型药物。细胞实验结果表明,低浓度的维生素 E-TPGS 对乳糜微粒的分泌有很强的增强作用。动物实验结果表明,维生素 E-TPGS 可通过与细胞实验结果一致的作用显著增强普罗布考的淋巴转运。然而,这种作用会在浓度依赖性增加后达到平台期并饱和。这些研究首次证明了维生素 E-TPGS 在亲脂性药物肠道淋巴转运中的作用,它可以显著促进肠上皮细胞乳糜微粒的分泌。