小鼠经鼻腔给药醒脑静微乳和mPEG2000-PLA修饰醒脑静微乳后体内栀子苷的动力学比较研究

Study on pharmacokinetics of geniposide in mice administrated by Xingnaojing microemulsion and mPEG2000-PLA modified Xingnaojing microemulsion

该实验建立了小鼠体内醒脑静微乳和mPEG2000-PLA修饰醒脑静微乳鼻腔给药后测定血浆栀子苷浓度的高效液相色谱法,探讨2种制剂经鼻腔给药后栀子苷在小鼠体内的药动学过程。将80只小鼠分为2组,分别鼻腔给药醒脑静微乳和mPEG2000-PLA修饰醒脑静微乳后,于不同时间点摘眼球取血,HPLC测定血浆中栀子苷的量,以Kinetica软件非房室模型拟合药动学参数。结果显示小鼠鼻腔给药醒脑静微乳后,血药主要药动学参数为Cmax(4.36±2.69)mg·L-1,tmax1 min,MRT(29.73±4.54)min,AUC(53.63±14.03)mg·L-1·min;小鼠鼻腔给药共聚物修饰醒脑静微乳后,血药主要药动学参数为Cmax(9.75±4.14)mg·L-1,tmax1 min,MRT(22.34±2.90)min,AUC(131.87±40.13)mg·L-1·min。与醒脑静微乳相比,共聚物修饰醒脑静微乳经小鼠鼻腔给药后,栀子苷入血程度更高,可能与其刺激性较小而吸收较多有关。

An HPLC method for the determination of geniposide concentration in mouse plasma was developed and the pharmacokinetics after intranasal administration of Xingnaojing microemulsion （XNJ-M） and mPEG2000-PLA modified Xingnaojing microemulsion （XNJ-MM） were investigated. Eighty mice were treated by XNJ-M and XNJ-MM nasally. The plasma samples were collected at different times and the drug in samples was detected by HPLC. The pharmacokinetic parameters were calculated by the software of Kinetica. The pharmacokinetic parameters of geniposideof XNJ-M were Cmax（4.36±2.69） mg·L^-1, tmax1 min, MRT（29.73±4.54）min, AUC（53.63±14.03） mg·L^-1·min. The pharmacokinetic parameters of geniposide of XNJ-MM were Cmax（9.75±4.14） mg·L^-1, tmax1 min, MRT（22.34±2.90） min, AUC（131.87±40.13） mg·L^-1·min. Geniposide can be absorbed into bloodin a higher degree after intranasal administration with XNJ-MM compared to XNJ-M, which maybe caused by its less irritating and more absorption.