杨梅素自组装胶束在大鼠体内的药动学及组织分布特性

Pharmacokinetics and tissue distribution of myricetin-loaded self-assembled micelles in rats

目的:探究杨梅素HS15胶束(MYR-Ms)在大鼠体内的药动学及组织分布特性。方法:以0.1%甲酸丙酮为蛋白沉淀剂,抗坏血酸为保护剂,血浆-丙酮(1∶9)作为提取剂处理样品;采用Agilent Zorbax Eclipse Plus C18色谱柱,以乙腈-0.1%甲酸水溶液(25∶75)为流动相,负离子模式,多重反应选择离子监测(MRM)方式(m/z 317→151.1),测定大鼠血浆及各组织中的药物浓度。结果:杨梅素(MYR)混悬液的绝对生物利用度仅为0.66%,肾脏药物浓度最高,远远高于其他组织(肾>肝>肺>脾>心);与MYR混悬液相比,MYR-Ms的绝对生物利用度为1.74%,AUC0-t提高2.63倍,血药浓度峰值(Cmax)提高12.24倍,各组织药物浓度均显著提高,且消除减慢,但组织分布靶向性降低。结论:将MYR制成HS15胶束后可显著提高MYR的生物利用度,且体内消除减慢,为进一步开发和应用MYR提供了参考。

OBJECTIVE To investigate the pharmacokinetics and tissue distribution of myricetin HS15 micelles(MYR-Ms)in rats.METHODS Acetone(containing 0.1%(V/V)formic acid)was used as protein precipitant,ascorbic acid was added as protective agent,and plasma-acetone(1∶9)was used as extractant for the sample preparation.An Agilent Zorbax Eclipse Plus C18 column was used for separation,acetonitrile-0.1%formic acid aqueous solution(25∶75)was used as the mobile phase for isocratic elution.The drug concentrations in rat plasma and tissues were determined by using multiple reaction monitoring(MRM)mode with negative ESI(m/z 317→151.1).RESULTS Absolute bioavailability of myricetin(MYR)suspension was only 0.66%,and the drug concentration in kidney was the highest,which was much higher than that in other tissues(kidney>liver>lung>spleen>heart).Compared with MYR suspension,the absolute bioavailability of MYR-Ms was 1.74%,AUC0-t of MYR-Ms was increased by 2.63-fold,and Cmax was increased by 12.24-fold.Drug concentration was markedly increased in tissues and elimination was slowed down,but the tissue distribution targeting of MYR-Ms decreased.CONCLUSION Myricetin HS15 micelles can significantly improve the bioavailability of MYR and slow down its elimination in vivo,which provide reference for further development and application of MYR.