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目的:比较黄芩苷(BA)、黄芩苷磷脂复合物(BA-PC)及黄芩苷磷脂复合物的两种自微乳给药系统(BA-PC-SMEDDS),即BA-PC-NS-SMEDDS(不含天然乳化剂)、BA-PC-NE-SMEDDS(含天然乳化剂)的吸收特性,预测其提高药物生物利用度的能力。方法:采用Caco-2细胞模型进行BA、BA-PC及BA-PC-SMEDDS的转运研究,HPLC色谱法测定BA含量。结果:BA的转运速率和Papp值随着浓度的增加而增加,表明药物很可能为被动吸收机制;随着时间的延长各浓度的转运速率和Papp值呈下降趋势。当加入P-gp抑制剂后,BA外排率(ER)由2.07降为0.48,减少了76.8%,证明BA为P-gp底物。BA、BA-PC及BA-PC-SMEDDS在90 min以前转运量无明显增加(P>0.05),而90 min之后,BA-PC及BA-PC-SMEDDS的转运量较BA有显著性增加(P<0.05),转运3 h时,累积转运量及Papp值的大小依次为:BA-PC-NS-SMEDDS>BA-PC-NE-SMEDDS>BA-PC>BA,并呈现显著性差异(P<0.05)。而且,BA-PC或BA-PC-SMEDDS吸收方向的Papp值均明显大于加入P-gp抑制剂(维拉帕米)的Papp值(P<0.05)。结论:PC促进了BA的跨膜转运,PC-SMEDDS相结合使转运效果进一步增强(P<0.05),其中,BA-PC-NS-SMEDDS促吸收的效果较BA-PC-NE-SMEDDS更显著(P<0.05)。
OBJECTIVE: To compare BA-PC-SMEDDS (BA-PC-NS-SMEDDS) with baicalin (BA), baicalin phospholipid complex (BA-PC) and baicalin phospholipid complex (Without natural emulsifier) and BA-PC-NE-SMEDDS (with natural emulsifier) to predict its ability to enhance drug bioavailability. Methods: The Caco-2 cell model was used to study the transport of BA, BA-PC and BA-PC-SMEDDS. The content of BA was determined by HPLC. Results: BA transport rate and Papp value increased with the increase of concentration, indicating that the drug is likely to be a passive absorption mechanism; with time prolonging the concentration of the transport rate and Papp value showed a downward trend. When P-gp inhibitor was added, BA efflux rate (ER) decreased from 2.07 to 0.48, a decrease of 76.8%, indicating that BA is a P-gp substrate. The transport volume of BA, BA-PC and BA-PC-SMEDDS did not increase significantly after 90 min (P> 0.05). After 90 min, BA-PC and BA-PC- (P <0.05). After transfused for 3 h, the cumulative transports and Papp values were in the order of BA-PC-NS-SMEDDS> BA-PC-NE-SMEDDS> BA- <0.05). Moreover, the Papp values in the BA-PC or BA-PC-SMEDDS uptake were significantly greater than those in the P-gp inhibitor (verapamil) (P <0.05). CONCLUSION: PC promoted the transmembrane transport of BA and the combination of PC-SMEDDS enhanced the translocation effect (P <0.05). BA-PC-NS-SMEDDS was more effective in promoting absorption than BA-PC-NE-SMEDDS (P <0.05).