The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, The Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China; Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
J Pharm Sci. 2013 Dec;102(12):4414-25. doi: 10.1002/jps.23758. Epub 2013 Oct 25.
Andrographolide (AND) is one of diterpenoids separated from Andrographis paniculata with a wide spectrum of biological activities of being anti-inflammatory, anticancer, hepatoprotective, and antihyperlipidemic. But its poor water solubility and instability resulted in lower bioavailability and seriously limited its pharmacological function. In this study, AND-loaded solid lipid nanoparticles (AND-SLNs) were prepared by a high-pressure homogenization method and presented as spherically shaped under transmission electron microscopy with an average diameter of 286.1 nm and zeta potential of -20.8 mV. The average drug-entrapment efficiency and drug loading were 91.00% and 3.49%, respectively. The results indicated that the lower bioavailability of AND is not only because of the poor solubility but also owing to its metabolic instability in intestinal segments. Furthermore, the transport mechanism of AND in Caco-2 cell model is complex in which an active transport carrier (P-glycoprotein) is involved in. The bioavailability and antihyperlipidemic activity of AND were improved by AND-SLNs by increasing the solubility and stability of AND in the intestine and by changing its transport mode in Caco-2 cell. The bioavailability of AND was increased to 241% by AND-SLNs as compared with AND suspension. AND-SLNs would be a promising drug-delivery system to enhance the oral absorption and bioavailability of AND.
穿心莲内酯（AND）是从穿心莲中分离得到的二萜类化合物之一，具有广泛的生物活性，包括抗炎、抗癌、保肝和抗高血脂。但其较差的水溶性和不稳定性导致其生物利用度较低，严重限制了其药理作用。本研究采用高压匀质法制备了穿心莲内酯固体脂质纳米粒（AND-SLNs），透射电镜下呈球形，平均粒径为 286.1nm，Zeta 电位为-20.8mV。平均药物包封率和载药量分别为 91.00%和 3.49%。结果表明，AND 的低生物利用度不仅与其溶解度差有关，还与其在肠道段的代谢不稳定性有关。此外，AND 在 Caco-2 细胞模型中的转运机制较为复杂，涉及一种主动转运载体（P-糖蛋白）。AND-SLNs 通过提高 AND 在肠道中的溶解度和稳定性，并改变其在 Caco-2 细胞中的转运方式，提高了 AND 的生物利用度和抗高血脂活性。与 AND 混悬液相比，AND-SLNs 使 AND 的生物利用度提高到 241%。AND-SLNs 有望成为一种增强 AND 口服吸收和生物利用度的药物传递系统。
