载葛根素的TPP阳离子/MMP肽双修饰脂质体的制备及其对心肌缺血/再灌注损伤的影响研究

Preparation of TPP cation/MMP peptide bimodified liposomes loaded with puerarin and its effects on myocardial ischemia/reperfusion injury

目的构建载葛根素的TPP阳离子/MMP肽双修饰脂质体(PUE@T/M-L),并研究其减少心肌缺血/再灌注(I/R)损伤的作用。方法合成TPP-PEG-PE和MMP-PEG-PE高分子材料来修饰脂质体,采用薄膜水化法制备PUE@T/M-L,考察其线粒体靶向性和溶酶体逃逸效果;构建心肌I/R损伤模型,评价PUE@T/M-L对心肌I/R损伤的作用。结果PUE@T/M-L呈圆球形结构,平均粒径为144 nm,Zeta电位为-19.4 mV,具有较好的线粒体靶向性和溶酶体逃逸效果。动物实验结果表明,PUE@T/M-L能显著减少心肌梗死面积,降低心肌细胞凋亡率,其减少心肌I/R损伤作用明显优于其他类型的脂质体,可能与MMP肽靶向和滞留于缺血心肌,再由TPP阳离子靶向递送进入心肌细胞线粒体有关。结论PUE@T/M-L可将药物高效递送至缺血心肌细胞线粒体,从而显著增强葛根素降低心肌I/R损伤的作用。

Objective To establish puerarin-carrying TPP cation/MMP peptide co-modified liposomes(PUE@T/M-L)and to determine their effect on myocardial ischemia/reperfusion(I/R)injury.Methods TPP-PEG-PE and MMP-PEG-PE target-head polymer materials were synthesized to modify liposomes.PUE@T/M-L was prepared by thin-film hydration to determine their mitochondrial targeting and lysosomal escape effect,to establish a model of myocardial I/R injury,and to evaluate the effect of PUE@T/M-L in reducing myocardial I/R injury.Results PUE@T/M-L showed a spherical structure with an average particle size of 144 nm and a zeta potential of-19.4 mV,with fair mitochondrial targeting and lysosomal escape effect.PUE@T/M-L largely reduced the area of myocardial infarction and the apoptosis rate of cardiomyocytes.The efficacy of PUE@T/M-L was obviously better than that of other liposomes,which might be related to MMP peptide targeting and retention in the ischemic myocardium,and then the target delivery into the mitochondria of cardiomyocytes by TPP cation.Conclusion PUE@T/M-L can efficiently deliver the drug into the mitochondria of ischemic cardiomyocytes,thus enhancing the drug effect on reducing myocardial I/R injury.