电致孔条件下青风藤提取液体内外透皮给药的相关性分析

Correlation Analysis of in Vitro and in Vivo Transdermal Delivery of Sinomenii Caulis Extracts Using Eletroporation

目的:研究电致孔条件下青风藤提取液体内、外透皮给药的最优电学参数组合,并对体内、外透皮给药的相关性进行分析。方法:在电致孔药物导入仪产生的多种电学参数下,体外实验利用高效液相色谱法检测透过小鼠离体皮肤后接受池中青藤碱的浓度;体内实验采用活体透皮仪进行,测定小鼠的血药浓度。通过正交试验分别得到体外和体内实验的电致孔最优电学参数组合,并对相同电致孔参数下的体外透过浓度(X)与体内血药浓度(Y)进行线性回归。结果:体外透皮给药的最优电学参数条件为脉冲时间1.2ms、脉冲电压300V、波形为正弦波、脉冲频率120个·min-1、脉冲数360个;体内透皮给药的最优电学参数条件为脉冲时间1.3ms、脉冲电压300V、波形为正弦波、脉冲频率120个·min-1、脉冲数360个,二者最优电学参数条件基本一致;回归方程为Y=0.657518X-16.255(r=0.9547),体内外相关性非常显著(α=0.001)。结论:此方法可以用于电致孔条件下药物透皮给药的体内、外相关性评价,有望为以后开发新型透皮给药系统提供参考依据。

OBJECTIVE：To explore the optimal electrical parameters of the transdermal delivery of Sinomenii Caulis extracts in vitro and in vivo using electroporation,and to analyze the correlation of transdermal delivery in vitro and in vivo.METHODS：Under the different electrical parameters of electroporation,the concentration of sinomenine across the rat skin in chamber diffusion cell was determined by HPLC in vitro.In vivo tests,the dermal apparatus for live rat was applied to determine the plasma concentration of mice.The optimal electrical parameters in vitro and in vivo were determined by the orthogonal experiment.The linear regression equation was figured through the sinomenine concentration in vitro（X） and the plasma concentration of Sinomenii Caulis in vivo（Y） under the same electrical parameters of electroporation.RESULTS：The optimal electrical parameters in vitro transdermal delivery were as follows：pulse duration of 1.2 ms,pulse voltage of 300 V,waveform of ED,pulse frequency of 120 pulse·min-1,pulse number of 360.The optimal in vivo were as follows：pulse duration of 1.3 ms,pulse voltage of 300 V,waveform of ED,pulse frequency of 120 pulse·min-1,pulse number of 360.The optimal electrical parameters of the two conditions were basically the same.The regression equation was Y=0.657 518X-16.255（r=0.954 7） and there was a high correlation between transdermal delivery in vitro and blood concentration in vivo（α=0.001）.CONCLUSION：This method can be used to evaluate the correlation between in vitro and in vivo transdermal delivery using electroporation,which is hoped to provide foundations for developing new transdermal drug delivery system.