Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
J Pharm Sci. 2013 Apr;102(4):1301-6. doi: 10.1002/jps.23460. Epub 2013 Feb 1.
The purpose of this study was to develop a high-drug-loading nanoemulsion by self-assembly to improve the oral absorption of high dosing poorly water-soluble drugs. Probucol was selected as a model drug and the probucol-loaded self-assembled nanoemulsion (PSN) was prepared and characterized. Moreover, the intestinal absorption and in vivo pharmacokinetic behavior of PSN were evaluated in rats after oral administration. The experimental results indicated that PSN was nanometer-sized droplets with the mean diameter of 40.32 ± 0.31 nm and polydispersity index of 0.184 ± 0.005. The aqueous solubility of probucol was remarkably increased after its incorporation into PSN. Compared with free drug suspension, the intestinal absorption of PSN was not significantly increased in duodenum, but obviously enhanced 3.62- and 13.1-fold in jejunum and ileum, respectively. In particular, the in vivo pharmacokinetic results indicated that the oral bioavailability of probucol was greatly improved 8.97-fold by PSN. Thereby, the high-drug-loading self-assembled nanoemulsion was very effective in enhancing the oral absorption of high-dosing poorly water-soluble drugs.
本研究旨在通过自组装开发一种高载药量的纳米乳，以提高高剂量难溶性药物的口服吸收。选择普罗布考作为模型药物，制备并表征了载普罗布考自组装纳米乳（PSN）。此外，还在大鼠体内评价了 PSN 经口服给药后的肠道吸收和体内药代动力学行为。实验结果表明，PSN 为纳米级液滴，平均直径为 40.32±0.31nm，多分散指数为 0.184±0.005。普罗布考在掺入 PSN 后其水溶解度显著增加。与游离药物混悬液相比，PSN 在十二指肠中的肠道吸收没有明显增加，但在空肠和回肠中分别显著增强了 3.62 倍和 13.1 倍。特别是，体内药代动力学结果表明，PSN 使普罗布考的口服生物利用度提高了 8.97 倍。因此，高载药量自组装纳米乳在增强高剂量难溶性药物的口服吸收方面非常有效。
