Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake.
Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake.
复制标题
自微乳化给药系统通过淋巴摄取提高石杉碱甲的生物利用度
DOI：
10.1016/j.apsb.2017.02.002
复制
发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Tang J
中科院分区：
文献类型：
--
作者：
Li F;Hu R;Wang B;Gui Y;Cheng G;Gao S;Ye L;Tang J
石杉碱甲（Hup-A）是一种难溶性药物，口服生物利用度低。采用自微乳化给药系统（SMEDDS）提高了石杉碱甲的口服生物利用度和淋巴吸收转运。采用单向肠灌流（SPIP）技术和乳糜微粒流阻断法研究其在肠吸收、肠系膜淋巴结分布和肠淋巴摄取。石杉碱甲自微乳给药系统的血药浓度-时间曲线下面积（AUC）显著高于石杉碱甲混悬液（P<0.01）。不同肠段的吸收速率常数（Ka）和表观渗透系数（Papp）表明，Hup-A在小肠中的吸收速率常数（Ka）和表观渗透系数（Papp）均为被动转运，回肠的Ka和Papp值均明显高于其它肠段。肠系膜淋巴结中石杉碱甲浓度的测定可用于解释石杉碱甲自微乳的肠淋巴吸收。Hup-A SMEDDS阻断模型的AUC和最大血药浓度（Cmax）显著低于对照模型（P<0.05）。Hup-A SMEDDS和Hup-A混悬液的淋巴转运比例分别约为40%和5%，表明SMEDDS能显著提高Hup-A的肠道淋巴吸收和转运。与石杉碱甲混悬液相比，自微乳给药系统能提高石杉碱甲的口服生物利用度和肠道吸收。通过对Hup-A在肠系膜淋巴结中浓度的测定和乳糜微粒流阻断实验，证实Hup-A自微乳经淋巴吸收。
Huperzine A (Hup-A) is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration–time curve (AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (P<0.01). The absorption rate constant (Ka) and the apparent permeability coefficient (Papp) for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values of Ka and Papp of Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration (Cmax) of the blocking model were significantly lower than those of the control model (P<0.05). The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%, respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A. Compared with the Hup-A suspension, SMEDDS formulation can enhance the oral bioavailability and intestinal absorption of Hup-A. According to the detection of Hup-A concentration in mesenteric lymph nodes and the results of the chylomicron flow blocking experiments, Hup-A SMEDDS was confirmed to be absorbed through the lymphatic route.