摘要
目的:探索盐酸法舒地尔脂质体的最佳制备方法,评价其对血管紧张素Ⅱ(AngⅡ)诱导的炎性内皮细胞的改善作用。方法:采用薄膜分散法制备盐酸法舒地尔脂质体,以包封率为评判标准优化制备方案,并检测其粒径及电位、模拟体外释放实验、细胞摄取等相关性质。体外培养人脐静脉内皮细胞(HUVECs),将其分为对照组、AngⅡ组、载药脂质体组及空白脂质体组,CCK8法观察载药脂质体对细胞活力的影响,硝酸还原法检测细胞培养上清液一氧化氮(NO)含量,酶联免疫吸附试验(ELISA)法测定细胞培养上清液中细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)含量。结果:盐酸法舒地尔脂质体平均粒径为(185.12±20.90)nm,平均电位为(-25.22±1.23)mV,包封率(91.48±5.46)%,载药量(41.86±2.35)%,体外模拟释放在24 h内可释放出约87.62%所包封的药物,能被细胞成功摄取。与AngⅡ组和空白脂质体组比较,载药脂质体组能明显减弱AngⅡ对内皮细胞活力的抑制作用,载药脂质体组NO含量升高,VCAM-1、ICAM-1含量降低(P<0.01)。结论:盐酸法舒地尔脂质体为纳米制剂,包封率及载药量高,能成功被HUVECs摄取,可达到长效缓释的效果,改善AngⅡ引起的内皮细胞炎性作用。
Objective:To explore the optimal preparation method of fasudil hydrochloride liposomes and to evaluate its ameliorative effect on angiotensinⅡ(AngⅡ)-induced inflammatory endothelial cells.Methods:Fasudil hydrochloride liposomes were prepared by the thin-film dispersion method,encapsulation rate was used as the criterion to optimize the preparation process,and the particle size,potential,simulated in vitro release assay,cellular uptake and other related properties were examined.Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and divided into control group,AngⅡgroup,drug-laden liposome group and blank liposome group.The effect of drug-laden liposomes on cell viability was observed by CCK8 method,nitric oxide(NO)content in cell culture supernatant was measured by nitrate reduction,and intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)content in cell culture supernatant were measured by enzyme-linked immunosorbent assay(ELISA).Results:The average particle size of fasudil hydrochloride liposomes was(185.12±20.90)nm,the average potential was(-25.22±1.23)mV,the encapsulation rate was(91.48±5.46)%,the drug loading capacity was(41.86±2.35)%,and about 87.62%of the encapsulated drug was released within 24 h in the in vitro simulation,which could be successfully taken up by the cells.Compared with the AngⅡgroup and the blank liposome group,significant attenuation of the inhibitory effect of AngⅡon endothelial cell viability was observed in the drug-laden liposome group,and the NO content increased while the VCAM-1 and ICAM-1 content decreased in the drug-laden liposome group(P<0.01).Conclusion:Fasudil hydrochloride liposomes are nanoparticles with high encapsulation rate and drug loading capacity.They can be successfully taken up by HUVECs,achieve long-acting and slow-release effects,and improve the AngⅡ-induced inflammation of endothelial cells.
作者
莫莹莹
李京涛
梁彬彬
吴棘
Mo Yingying;Li Jingtao;Liang Binbin;Wu Ji(Department of Ultrasound,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)
出处
《广西医科大学学报》
CAS
2022年第9期1371-1376,共6页
Journal of Guangxi Medical University
基金
国家自然科学基金资助项目(No.81760314)
广西医学高层次人才“139”计划(No.G201903014)。
