【摘要】 目的:制备和表征甘草次酸(GA)纳米粒,并评价其体外抗肿瘤活性。方法:以聚乙烯吡咯烷酮K30为载体,使用反溶剂沉淀-冷冻干燥法制备GA纳米粒。采用X射线衍射分析、红外光谱分析、差示扫描量热分析、粒度分析等方法对所制纳米粒进行表征;采用高效液相色谱法测定纳米粒中GA的溶解度和载药量;采用MTT法考察GA原料药及纳米粒(GA剂量均为12.5、25、50、100、200μmol/L)对人肝癌细胞HepG2的体外抑制活性并计算半数抑制浓度(IC50)。结果:所制纳米粒中GA的X射线衍射特征峰和红外特征吸收峰均消失,吸热峰发生改变。纳米粒的粒径为(194.88±23.52)nm,低于原料药的(2 592.33±207.51)nm;分散指数为0.24±0.04,高于原料药的0.15±0.03;纳米粒的平均载药量为15.99%;溶解度由原料药的(1.05±0.01)μg/mL升至(250.00±0.15)μg/mL。体外抗肿瘤试验结果显示,GA原料药200μmol/L组和纳米粒各剂量组的细胞存活率均较空白对照组显著降低,且GA纳米粒各剂量组(除12.5μmol/L组外)的细胞存活率均显著低于同剂量原料药组(P<0.01);GA纳米粒的IC50值为86.3μmol/L,低于原料药的364.4μmol/L。结论:成功制得GA纳米粒;所制纳米粒粒径小且分布均匀,溶解度增大且体外抗肿瘤活性增强。更多还原

【Abstract】 OBJECTIVE:To prepare and characterize glycyrrhetinic acid(GA) nanoparticles,and to evaluate its in vitro anti-tumor activity. METHODS:Using PVP K30 as carrier,GA nanoparticles were prepared by anti-solvent precipitation and freeze-drying method. X-ray diffraction,infrared spectrum,differential scanning calorimetry and granularity analysis were used to characterize the nanoparticles; HPLC method was used to measure the solubility and drug-loading amount of GA in the nanoparticles. MTT method was used to assay the in vitro inhibition activity of GA raw material and nanoparticles(GA doses were12.5,25,50,100,200 μmol/L)on human liver cancer cell HepG2 and calculate its IC50. RESULTS:The characteristic peaks of X-ray diffraction and infrared absorption of GA disappeared in the nanoparticles and the endothermic peak changed. The particle size of the nanoparticles was(194.88±23.52)nm,which was lower than(2 592.33±207.51)nm of raw material. The dispersion index was 0.24±0.04,which was higher than 0.15±0.03 of raw material. The average drug-loading amount of GA was 15.99%.Moreover,the solubility of nanoparticles increased from(1.05±0.01)μg/mL to(250.00±0.15)μg/mL. The results of antitumor test in vitro showed that the cell survival rates in the group of GA raw material 200 μ mol/L and GA nanoparticles groups were significantly lower than that in blank control group,and the cell survival rates of GA nanoparticles groups(except for 12.5 μmol/L group) were significantly lower than that of same dose group of raw material(P<0.01). IC50 of GA nanoparticles was 86.3μmol/L,which was lower than 364.4 μmol/L of raw material. CONCLUSIONS:GA nanoparticles are prepared successfully;the prepared nanoparticles have small size and uniform distribution,and the solubility are increased and antitumor activity in vitro are enhanced.更多还原