Liu Xin-Yi, Jiang Zhong-Biao, Luo Jie, Li Jian-He, Hu Xiong-Bin
Department of Pharmacy, the Second Xiangya Hospital, Central South University Changsha 410011, China.
Department of Radiology, the Second Xiangya Hospital, Central South University Changsha 410011, China.
Zhongguo Zhong Yao Za Zhi. 2019 Jun;44(11):2244-2250. doi: 10.19540/j.cnki.cjcmm.20190321.302.
PUE@PEG-PLGA micelles has excellent characteristics such as small particle size, high drug loading and slow drug release. The results of TEM electron microscopy showed that PUE@PEG-PLGA micelles had obvious core-shell structure. The critical micelle concentration(CMC) of PEG-PLGA micelles determined by pyrene assay was about 4.8 mg·L~(-1). Laser confocal experiments showed that PEG-PLGA micelles can enhance the cellular uptake of coumarin-6 and aggregate around the mitochondria; quantitative results of extracellular drug residues also indirectly confirmed that PEG-PLGA micelles can promote cellular uptake of the drug. Acute ischemic myocardial model rats were prepared by coronary artery ligation, and then the model rats were randomly divided into six groups: Sham operation group, model group, puerarin(PUE) group, as well as low-, mid-, and high-dose PUE@PEG-PLGA micelles groups. Drugs were given by iv administration 5 min after the ligation. The ST segment changes in the electrocardiogram were monitored; serum creatine kinase(CK), lactate dehydrogenase(LDH), aspartate aminotransferase(AST), and malondialdehyde(MDA) levels were detected and myocardial infarct size was also measured. Both PUE and PUE@PEG-PLGA micelles can reduce the elevated ST segment, reduce serum CK, LDH, AST and MDA levels, and reduce myocardial infarct size. The efficacy of PUE@PEG-PLGA medium and high dose groups was significantly better than that in the PUE group, and the efficacy in PUE@PEG-PLGA low dose group was basically equivalent to that in the PUE group. PUE@PEG-PLGA micelles can greatly improve the cardiomyocytes uptake of PUE, enhance the anti-acute myocardial ischemia effect of drugs, and reduce its dosage.
葛根素@聚乙二醇-聚乳酸-羟基乙酸共聚物胶束具有粒径小、载药量高和药物缓释等优异特性。透射电子显微镜结果显示，葛根素@聚乙二醇-聚乳酸-羟基乙酸共聚物胶束具有明显的核壳结构。通过芘测定法测定的聚乙二醇-聚乳酸-羟基乙酸共聚物胶束的临界胶束浓度（CMC）约为4.8 mg·L⁻¹。激光共聚焦实验表明，聚乙二醇-聚乳酸-羟基乙酸共聚物胶束可增强香豆素-6的细胞摄取并在线粒体周围聚集；细胞外药物残留的定量结果也间接证实聚乙二醇-聚乳酸-羟基乙酸共聚物胶束可促进药物的细胞摄取。通过冠状动脉结扎制备急性缺血性心肌模型大鼠，然后将模型大鼠随机分为六组：假手术组、模型组、葛根素（PUE）组以及低、中、高剂量葛根素@聚乙二醇-聚乳酸-羟基乙酸共聚物胶束组。结扎后5分钟通过静脉注射给药。监测心电图中的ST段变化；检测血清肌酸激酶（CK）、乳酸脱氢酶（LDH）、天冬氨酸转氨酶（AST）和丙二醛（MDA）水平，并测量心肌梗死面积。葛根素和葛根素@聚乙二醇-聚乳酸-羟基乙酸共聚物胶束均可降低升高的ST段，降低血清CK、LDH、AST和MDA水平，并减小心肌梗死面积。葛根素@聚乙二醇-聚乳酸-羟基乙酸共聚物中、高剂量组的疗效明显优于葛根素组，葛根素@聚乙二醇-聚乳酸-羟基乙酸共聚物低剂量组的疗效与葛根素组基本相当。葛根素@聚乙二醇-聚乳酸-羟基乙酸共聚物胶束可大大提高心肌细胞对葛根素的摄取，增强药物的抗急性心肌缺血作用，并降低其用量。
