Zhang Huiyun, Wang Qilong, Sun Congyong, Zhu Yuan, Yang Qiuxuan, Wei Qiuyu, Chen Jiaxin, Deng Wenwen, Adu-Frimpong Michael, Yu Jiangnan, Xu Ximing
Center for Nano Drug/Gene Delivery and Tissue Engineering, Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
Pharmaceutics. 2019 Mar 6;11(3):107. doi: 10.3390/pharmaceutics11030107.
：6-shogaol is a promising anti-cancer and anti-inflammatory agent. However, the treatment effectiveness of 6-shogaol is limited by poor water solubility, poor oral absorption and rapid metabolism. Herein, 6-shogaol loaded in micelles (SMs) were designed to improve 6-shogaol's solubility and bioavailability. The micelles of a PEG derivative of linoleic acid (mPEG-LA) were prepared by the nanoprecipitation method with a particle size of 76.8 nm, and entrapment of 81.6 %. Intriguingly, SMs showed a slower release in phosphate buffer saline (PBS) (pH = 7.4) compared to free 6-shogaol while its oral bioavailability increased by 3.2⁻fold in vivo. More importantly, the in vitro cytotoxic effect in HepG2 cells of SMs was significantly higher than free 6-shogaol. Furthermore, SMs could significantly improve the tissue distribution of 6-shogaol, especially liver and brain. Finally, SMs showed a better hepatoprotective effect against carbon tetrachloride (CCl4)-induced hepatic injury in vivo than free 6-shogaol. These results suggest that the novel micelles could potentiate the activities of 6-shogaol in cancer treatment and hepatoprotection.
6-姜辣素是一种很有前景的抗癌和抗炎药物。然而，6-姜辣素的治疗效果受到其水溶性差、口服吸收不良和代谢迅速的限制。在此，设计了负载6-姜辣素的胶束（SMs）以提高6-姜辣素的溶解度和生物利用度。通过纳米沉淀法制备了亚油酸聚乙二醇衍生物（mPEG-LA）胶束，粒径为76.8 nm，包封率为81.6%。有趣的是，与游离6-姜辣素相比，SMs在磷酸盐缓冲盐水（PBS，pH = 7.4）中的释放较慢，而其体内口服生物利用度提高了3.2倍。更重要的是，SMs在HepG2细胞中的体外细胞毒性作用明显高于游离6-姜辣素。此外，SMs可以显著改善6-姜辣素的组织分布，尤其是肝脏和大脑。最后，在体内，SMs对四氯化碳（CCl4）诱导的肝损伤显示出比游离6-姜辣素更好的肝保护作用。这些结果表明，这种新型胶束可以增强6-姜辣素在癌症治疗和肝保护方面的活性。
