School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
Guangzhou University of Chinese Medicine, Neihuan Xilu, Guangzhou Daxuecheng, Guangzhou, China.
Phytomedicine. 2018 May 15;44:1-8. doi: 10.1016/j.phymed.2018.04.022. Epub 2018 Apr 10.
Vinegar baked Radix Bupleuri (VBRB) is a wildly used traditional Chinese medicine, it could be used as a meridian guided drug to enhance liver targeting efficiency of the delivered drug in addition to its therapeutic effect.
To investigate the liver targeting effect induced by VBRB via coadministration with 10-Hydroxycamptothecin loaded polymeric micelles.
First of all, the inhibitory effect of VBRB on the activity of glutathione S-transferase (GST) was investigated in vitro to select the most effective extract. After oral administration of 10-Hydroxycamptothecin (HCPT) polymeric micelles with low, medium and high doses of VBRB, pharmacokinetic parameters, including the ratio of Cmax in the liver (Ce) and the relative uptake efficiency (RUE), were employed to assess the liver targeting efficiency.
It was found that VBRB extract BC1 has the strongest inhibition effect on GST activity in the five extracts. By coadministration of HCPT loaded micelles with three doses of BC1, the AUC of HCPT in the liver raised by 42.5%, 23.0%, -0.2%, with RUE 1.45, 1.23, 1.02 for low, medium and high dose groups, respectively, indicating that low and medium dose of BC1 presented better liver-targeting enhancing effect than that of the high dose, which corresponded to the commonly used dose of VBRB in traditional Chinese medicine formulae.
VBRB could effectively enhance the liver-targeting efficiency of HCPT loaded polymeric micelles after oral coadministration. Such a simple but effective strategy may enlighten on the potential use of meridian guided drug together with modern drug delivery system to achieve better active drug targeting.
醋炙柴胡（VBRB）是一种广泛使用的中药，除了其治疗效果外，还可以用作引导药物归经的药物，以提高所输送药物的肝靶向效率。
研究醋炙柴胡与载 10-羟基喜树碱的聚合物胶束共同给药诱导肝靶向的效果。
首先，体外考察 VBRB 对谷胱甘肽 S-转移酶（GST）活性的抑制作用，以选择最有效的提取物。在口服低、中、高剂量 VBRB 的载 10-羟基喜树碱（HCPT）聚合物胶束后，采用药代动力学参数，包括肝 Cmax 比值（Ce）和相对摄取效率（RUE），评价肝靶向效率。
发现 5 种提取物中，BC1 提取物对 GST 活性的抑制作用最强。与 HCPT 载药胶束共同给予 3 种剂量的 BC1 后，HCPT 在肝中的 AUC 分别增加了 42.5%、23.0%、-0.2%，低、中、高剂量组的 RUE 分别为 1.45、1.23、1.02，表明低、中剂量的 BC1 比高剂量具有更好的肝靶向增强作用，这与中药方剂中常用的 VBRB 剂量相对应。
口服共同给予 VBRB 可有效增强载 10-羟基喜树碱聚合物胶束的肝靶向效率。这种简单但有效的策略可能为将引导药物归经与现代药物传递系统相结合以实现更好的主动药物靶向提供启示。
