染料木素甲氧基封端的聚乙二醇-乳酸羟基乙酸共聚物胶束在小鼠体内的组织分布研究  

Tissue Distribution Study of Genistein-loaded Me PEG-PLGA Copolymer Micelle in Mice

作　　者：何礼[1] 金虹[1] 韩瑞伟[1] 阎雪莹[2] HE Li;JIN Hong;HAN Ruiwei;YAN Xueying(School of Pharmacy,Sichuan College of TCM,Sichuan Mianyang 621000,China;College of Pharmacy,Heilongjiang University of TCM,Harbin 150040,China)

机构地区：[1]四川中医药高等专科学校药学院,四川绵阳621000 [2]黑龙江中医药大学药学院,哈尔滨150040

出　　处：《中国药房》2018年第11期1496-1500,共5页China Pharmacy

基　　金：黑龙江省教育厅研究生创新科研项目(No.YJSCX2011-459HLJ);四川中医药高等专科学校科研项目(No.17ZRYB01)

摘　　要：目的:研究染料木素甲氧基封端的聚乙二醇-乳酸羟基乙酸(Me PEG-PLGA)共聚物胶束在小鼠体内的组织分布特征。方法:采用高效液相色谱法测定染料木素在小鼠血浆及各组织(心、肝、脾、肺、肾)中的浓度。色谱柱为Dikma Diamonsil C18,流动相为甲醇-水(60∶40,V/V),流速为1.0 m L/min,检测波长为260 nm,柱温为35℃,进样量为10μL。48只小鼠分为乳剂组和胶束组,每组24只,分别按40 mg/kg剂量尾静脉注射染料木素乳剂或染料木素Me PEG-PLGA共聚物胶束,检测给药后5、30、90 min血浆及各组织(心、肝、脾、肺、肾)中染料木素的含量,比较两组AUC_(0-90 min)和平均驻留时间(MRT)。结果:胶束组小鼠给药后5、30、90min血浆中染料木素的含量均高于乳剂组,给药后5、30 min肝组织中染料木素的含量均低于乳剂组。与乳剂组比较,胶束组小鼠血浆中染料木素的AUC_(0-90 min)明显增加、MRT明显延长(P<0.01),肝组织中染料木素的AUC_(0-90 min)明显降低、MRT明显缩短(P<0.05),肾组织中染料木素的AUC_(0-90 min)明显增加(P<0.05),其他差异均无统计学意义(P>0.05)。结论:染料木素制成Me PEGPLGA共聚物胶束后,可增加血浆中染料木素的分布,降低其在肝组织中分布,从而可能会提高治疗效果并降低药物肝毒性。OBJECTIVE：To study in vivo tissue distribution of genistein-loaded Me PEG-PLGA copolymer micelle in mice.METHODS：HPLC method was used to determine the concentrations of genistein in plasma and tissues（heart,liver,spleen,lung, kidney） of mice. The determination was performed on Dikma Diamonsil C18 colunm with mobile phase consisted of methanol-water（60 ∶ 40,V/V） at the flow rate of 1.0 m L/min. The detection wavelength was set at 260 nm,and the column temperature was 35 ℃. The sample size was 10 μL. 48 mice were divided into emulsion group and micelle group,with 24 mice in each group. They were given 40 mg/kg genistein emulsion or genistein-loaded Me PEG-PLGA copolymer micelle via tail vein. The contents of genistein in plasma and tissues（heart,liver,spleen,lung,kidney） were detected 5,30,90 min after medication.AUC_（0-90 min） minand mean residence time（MRT）were compared. RESULTS：The content of genistein in micelle group was higher than emulsion group 5,30,90 min after medication,and the content of genistein in liver tissue was lower than emulsion group 5,30 min after medication. Compared with emulsion group,AUC0-90 min minand MRT of genistein in plasma of mice in micelle group were increased significantly（P〈0.01）;AUC0-90 min minand MRT of genistein in liver tissue were decreased significantly（P〈0.05）. AUC0-90 min min of genistein in renal tissue was increased significantly（P〈0.05）,without statistical significance of other differences（P〉0.05）.CONCLUSIONS：genistein-loaded Me PEG-PLGA copolymer micelle can increase the distribution of genistein in plasma,reduce the distribution of it in liver tissue so as to improve therapeutic efficacy and reduce drug hepatotoxicity.

关 键 词：染料木素 甲氧基封端的聚乙二醇-乳酸羟基乙酸共聚物胶束 小鼠 组织分布 

分 类 号：R965[医药卫生—药理学]