摘要
目的探索川芎嗪聚乙二醇-聚乳酸羟基乙酸共聚物(PEG-PLGA)纳米胶束在急性心肌缺血模型大鼠体内的组织分布。方法采用(PEG-PLGA)纳米胶束包载川芎嗪,制备川芎嗪PEG-PLGA纳米胶束,对载药系统进行表征,采用体外释药和急性心肌缺血模型大鼠体内的组织分布试验对该载药系统进行评价。结果川芎嗪PEG-PLGA纳米胶束粒径为(15.8±0.9)nm,Zeta电势为-(20.5±0.4)mV,载药量电镜结果表明川芎嗪PEG-PLGA纳米胶束明显的圆球形结纳米胶束呈现良好的光束,散射良好;体外释药试验发现川芎嗪PEG-PLGA纳米胶束释药缓慢,组织分布试验发现川芎嗪PEG-PLGA纳米胶束在正常大鼠脏器中AUC分布大小表现为肺>肝>脾>心≈肾>脑,但是,该纳米胶束在急性心肌缺血模型大鼠中AUC分布大小却表现为肺>肝>心>脾>肾>脑,川芎嗪PEG-PLGA心脏中的1.68倍,且差异有统计学意义(P <0.05)。结论这些结果表明川芎嗪PEG-PLGA纳米胶束具有良好的载药性能和缓释药物特点,可将药物蓄积于缺血心肌,具有良好的心脏靶向性。
Objective To prepare tetramethylpyrazine(TMP)PEG-PLGA micelles by encapsulation of TMP in polyethylene glycol-poly(lactide-co-glycolide)micelles and explore its tissue distribution characteristics in acute myocardial ischemia model rats. Methods TMP-PEG-PLGA micelles were prepared,and the drug delivery system was characterized. The in vitro release assay and tissue distribution of the acute myocardial ischemia rat were used to evaluate this drug delivery system. Results The particle size of TMP-PEG-PLGA nanomicelles was (15.8 ± 0.9)nm;Zeta potential -(20.5 ± 0.4)mV;drug loading(4.8 ± 0.5)%,and the entrapment efficiency (86.2 ± 4.1)%. The TEM electron microscopy results showed that the TMP-PEG-PLGA micelles had a pronounced spherical structure,and the Tyndall phenomenon showed that the TMP-PEG-PLGA micelles exhibited a good beam with good scattering. The in vitro release test found that the TMP-PEG-PLGA micelles released slowly;tissue distri- bution experiments showed that the AUC of TMP-PEG-PLGA micelles in normal rats in the lung was the biggest, followed by in the liver,spleen,heart or kidney and brain,while the AUC of tissue distribution of TMP-PEG- PLGA micelles in rats with acute myocardial ischemia in the lung was the biggest,followed by in the liver,heart, spleen,kidney and brain. The AUC of TMP-PEG-PLGA nanomicelles in rats with acute myocardial ischemia was 1.68 times than that of normal rat hearts,and there was significant difference(P < 0.05). Conclusion TMP-PEG- PLGA micelles have good drug-loading properties and sustained-release drug characteristics,and can accumulate drugs in ischemic myocardium and have good cardiac targeting.
作者
许璨
刘厂辉
彭旷
XU Can;LIU Changhui;PENG Kuang(Department of Cardiology,the First Affiliated Hospital of South China University,Hengyang 421001,China)
出处
《实用医学杂志》
CAS
北大核心
2019年第6期868-873,共6页
The Journal of Practical Medicine
基金
湖南省卫计委项目(编号:C201800145)
