甘草次酸长循环固体脂质纳米粒的制备与体外性能研究

摘要

OBJECTIVE: To prepare Glycyrrhetinic acid long-circulating solid lipid nanoparticles (GA-LSLN) and to investigate its properties in vitro. METHODS: GA-LSLN was prepared by emulsion-solvent evaporation-high pressure homogenization method. The size, Zeta potential, encapsulation efficiency and drug loading of GA-SLN were measured. The in vitro drug release of GA-LSLN was studied. SK-Hep-1 and MV 4-11 were treated with DEXA, GA and GA-LSLN. The cytotoxicity of GA-LSLN were evaluated by MTT method. RESULTS: The size, Zeta potential, encapsulation efficiency and drug loading of GA-LSLN were 103.1 nm, -36.2 mv, 94.6% and 11.3% , respectively. The release profile fitted well to the first-order rate process. The IC? Of DEXA, GA and free GA-LSLN to SK-Hep-1 were (199 ± 10) ,(32 ± 7), (141 ±5) umol-L~'. The Icso of them to MV 4-11 were (25 ± 3), (20 ± 5), (63 + 4) umol-L1. CONCLUSION: The GA-LSLN has sound particle size, high encapsulation efficiency and drug loading amount, and show sustained-release effect. GA and GA-LSLN show good cytotoxicity to SK-Hep-1 and MV 4-11.%目的:制备甘草次酸长循环固体脂质纳米粒(GA-LSLN),并对其体外性能进行考察.方法:采用乳化溶剂挥发-高压匀质法制备GA-LSLN,测定其粒径、Zeta电位、包封率和载药量,并对其体外释药进行研究；同时以地塞米松(DEXA)、游离甘草次酸(GA)和GA-LSLN作用于肝癌细胞SK-Hep-1和急性髓细胞白血病细胞MV 4-11,采用MTT法考察细胞毒性.结果:GA-LSLN的平均粒径为130.1nm,Zeta电位为-36.2 mV,包封率为94.6％,载药量为11.3％,其体外释放规律符合一级速率过程.DEXA、GA和GA-LSLN对SK-Hep-1细胞的半数抑制浓度(IC50)分别为(199±10)、(32±7)、(141±5)μmol· L-1,对MV 4-11的IC50分别为(25±3)、(20±5)、(63±4) μmol· L-1.结论:制备的GA-LSLN粒径、包封率和载药量均较理想,药物能达到缓释的作用,GA和GA-LSLN对肝癌细胞和白血病细胞均有较强的细胞毒性.