黄芩苷及其磷脂复合物、自微乳的Caco-2细胞跨膜转运研究

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(P0.05),而90 min之后,BA-PC及BA-PC-SMEDDS的转运量较BA有显著性增加(P0.05),转运3 h时,累积转运量及Papp值的大小依次为:BA-PC-NS-SMEDDSBA-PC-NE-SMEDDSBA-PCBA,并呈现显著性差异(P0.05)。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(P0.05)。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(P0.05),其中,BA-PC-NS-SMEDDS促吸收的效果较BA-PC-NE-SMEDDS更显著(P0.05)。

Drug Delivery Systems of Baicalin,Baicalin-phospholipid Complex and Self-microemulsifying Drug Across Caco-2 Cell Model

Objective:To study the absorption of baicalin(BA),baicalin-phospholipid complex(BA-PC),and two kinds of self-microemulsifying drug delivery system(SMEDDS) of BA-PC(BA-PC-NE-SMEDDS with natural emulsifier and BA-PC-NS-SMEDDS with nonionic surfactants) and predict the ability of improving bioavailability through changing the formulation of BA.Methods:Transmembrane transports of each formulation were studied by Caco-2 cell model and the concentration of BA was determined by HPLC.Results:With the increasing concentration of BA,the transport rate and apparent permeability coefficient(Papp) of BA was increased,indicating the passive absorption mechanism of BA.While with the increase of transport time,the transport rate and Papp of BA was decreased slowly,most likely due to the biological transformation of BA during the permeation process as reported in other people′s paper.When coupled with P-gp inhibitor(Verapamil),the efflux rate(ER) of BA decreased from 2.07 to 0.48,indicating it was the substrate of P-gp.Compared with BA,the cumulative permeate quantity of BA-PC and BA-PC-SMEDDS were with no significant increase before 90 min(P>0.05),but increased obviously after 90 min(P<0.05).Three hours later,the cumulative permeate quantity and Papp showed significant differences(P<0.05) among each formulation and were arranged in the following order:BA-PC-NS-SMEDDS>BA-PC-NE-SMEDDS>BA-PC>BA.Furthermore,the Papp of BA-PC and BA-PC-SMEDDS was significantly greater than that of BA coupled with Verapamil(P<0.05).Conclusion:PC promotes the permeation of BA;PC-SMEDDS further accelerates its permeation bases on BA-PC;And BA-PC-NS-SMEDDS shows the better effect than BA-PC-NE-SMEDDS to promote the permeation of BA.