基于双位点同步微透析技术的青藤碱微乳凝胶皮肤及血液药代动力学研究

Pharmacokinetic Study of Skin and Blood of Sinomenine-Loaded Microemulsion Gel Based on Double Sites Simultaneous Microdialysis

目的采用双位点同步微透析技术研究青藤碱微乳凝胶(Sinomenine-loaded microemulsion gel,SMG)的大鼠皮肤与血液药代动力学过程,探究SMG的经皮药代动力学特征。方法建立青藤碱的超高液相色谱(UPLC)含量测定方法,开展专属性、线性、精密度、回收率等方法学考察。SD大鼠经麻醉,腹部脱毛处理后,植入线性探针和血液探针,局部涂抹青藤碱微乳凝胶,采用微透析技术结合UPLC技术测定皮肤和血液透析液中青藤碱浓度。结果青藤碱的UPLC分析方法在0.5~20μg·mL^(-1)浓度范围内线性良好,色谱的专属性、精密度及回收率等均符合微透析样品检测要求。药代动力学研究中青藤碱在皮肤中C_(max)为(10.91±3.05)μg·mL^(-1),T_(max)为(180.00±39.80)min,AUC_(0→t)为(736.51±45.30)μg·min·mL^(-1);在血液中C_(max)为(6.74±1.91)μg·mL^(-1),T_(max)为(239.98±40.85)min,AUC_(0→t)为(426.43±30.18)μg·min·mL^(-1)。结论SMG经皮给药后能够缓慢持续释放青藤碱,可在皮肤中形成储库效应。

OBJECTIVE To investigate the pharmacokinetics of sinomenine-loaded microemulsion gel(SMG)by skin and blood microdialysis in rats,and explore the pharmacokinetic characteristics of SMG.METHODS An UPLC method for the determination of sinomenine was established,and its specificity,linearity,precision and recovery rate were examined.The probe was implanted after the rats were anesthetized and depilated,then the sinomenine microemulsion gel was applied onto the bare abdominal skin of the rats.The microdialysis technique and UPLC were used to determine the concentration of the drug.RESULTS The results showed that the established method for the determination of sinomenine microemulsion gel was well linear in the range of 0.5-20μg·mL^(-1),and the specificity,degree of precision and recovery rate of the chromatography all conformed to the examination requirements of microdialysis samples.The results of pharmacokinetic study showed that the C_(max) values of sinomenine in skin and blood were(10.91±3.05)and(6.74±1.91)μg·mL^(-1),respectively.The T_(max) values were(180.00±39.80)and(239.98±40.85)min,respectively.And the AUC_(0→t) values were(736.51±45.30)and(426.43±30.18)μg·min·mL^(-1).CONCLUSION The sinomenine microemulsion gel plays a role in forming skin reservoir through percutaneous penetration,and can control the sustained release of drug.