葛根素PEG-PE纳米胶束的制备及在急性心肌缺血模型小鼠体内的组织分布

Preparation of Puerarin-loaded PEG-PE Nano-micelles and Its Tissue Distribution in Acute Myocardial Ischemia Model Mice

目的制备葛根素聚乙二醇衍生化磷脂酰乙醇胺(PEG-PE)纳米胶束,并研究其在急性心肌缺血模型小鼠体内的组织分布特点。方法采用薄膜水化法制备葛根素PEG-PE纳米胶束,昆明小鼠60只,随机分成2组,每组30只,均尾静脉注射给予葛根素PEG-PE纳米胶束,剂量为20 mg·kg^(-1),给药5 min后,一组设为正常小鼠,另一组小鼠结扎冠脉造成急性心肌缺血模型。分别于给药后30、60、90、120、150和180 min处死部分动物,取心、肝、脾、肺、肾、脑等脏器,测定2组小鼠组织中葛根素的浓度。结果葛根素PEG-PE纳米胶束粒径约为25 nm,Zeta电位约为-3 m V,载药量约为(5.8±1.3)%,包封率约为(78.6±5.7)%;葛根素PEG-PE纳米胶束在正常小鼠脏器中AUC大小顺序为肝>肾>心>脾>肺>脑,而在急性心肌缺血模型小鼠中的AUC大小顺序为肝≈心>肾>肺>脾>脑,经计算模型小鼠心脏中的AUC为正常小鼠心脏中的1.9倍,且存在显著性差异(P<0.05)。结论葛根素PEG-PE纳米胶束具有良好的载药性能,其在心肌梗死早期区域具有较好的心脏靶向性,可以将药物蓄积于缺血心肌,为该药的进一步开发研究提供重要的参考依据。

OBJECTIVE To prepare puerarin-loaded PEG-PE nano-micelles and explore its tissue distribution in acute myo- cardial ischemia model mice. METHODS Puerarin-loaded PEG-PE nano-micelles were prepared by thin-film hydration meth- od. Sixty KM mice were randomly divided into two groups （30 in each group）. Both were given puerarin-loaded PEG-PE nano- mieelles at a dose of 20 mg kg-1. After 5 min of medication, the mice in one group were treated with ligation of coronary artery to establish acute myocardial ischemia, and the other one group was taken as the control. The animals were executed at 30, 60, 90, 120, 150 and 180 min, then the heart, liver, spleen, lung, and kidney were extracted. The content of puerarin in the organ tissue was determined by HPLC. RESULTS The drug loading and drug encapsulation of puerarin-loaded PEG-PE nano-micelles were （5.8 ± 1.3）% and （78.6 ±5.7）% , respectively, and the diameters and Zeta potential were 25 nm and - 3 mV, re- spectively. The AUCs of tissue distribution of puerarin-loaded PEG-PE nano-micelles in the control group were in the sequence of liver 〉 kidney 〉 heart 〉 spleen 〉 lung 〉 brain. While the AUCs of tissue distribution of PEGylated puerarin in acute myocardial isehemia model mice were in the sequence of liver~ heart 〉 kidney 〉 lung 〉 spleen 〉 brain. The AUCheart of puerarin-loaded PEG- PE nano-micelles in acute myocardial ischemia model mice was 1.9 times of that of the control mice （ P 〈 0.05 ）. CONCLU- SION Puerarin-loaded PEG-PE nano-micelles show excellent drug loading capabilities. It has good heart-targeting property in early myocardial infarction area and can accumulate in the ischemie myocardium. This study provides important information for further development of prepamiceion.