甘草次酸长循环固体脂质纳米粒的制备与体外性能研究

Study on the Preparation and in Vitro Properties of Glycyrrhetinic Acid Long-circulating Solid Lipid Nanoparticles

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MV4-11,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-36.2mV,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MV4-11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。

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 IC50 of DEXA,GA and free GA-LSLN to SK-Hep-1 were（199±10）,（32±7）,（141±5）μmol·L-1.The IC50 of them to MV 4-11 were（25±3）,（20±5）,（63±4）μmol·L-1.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.