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(2592.33±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。
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 were 12.5,25,50,100,200μmol/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(2592.33±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 200μmol/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 12.5μmol/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 364.4μmol/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.
作者
张丽娟
喻红梅
张勇
龚宁波
ZHANG Lijuan;YU Hongmei;ZHANG Yong;GONG Ningbo(Dept.of Clinical Medicine,Yanjing Medical College,Capital Medical University,Beijing 101300,China;Drug Crystal Form Research Center,Institute of Materia Medica,Chinese Academy of Medical Sciences/Peking Union Medical College,Beijing 100050,China;Dept.of Pharmacology,College of Basic Medicine and Life Sciences,Hainan Medical University,Haikou 571199,China)
出处
《中国药房》
CAS
北大核心
2020年第13期1589-1594,共6页
China Pharmacy
基金
国家科技重大专项(民口)课题(No.2018ZX09711-001)
中国医学科学院医学与健康科技创新工程项目(No.2017-I2M-1-010)
首都医科大学燕京医学院科研培育基金(No.18qdky02)。
关键词
甘草次酸纳米粒
反溶剂沉淀-冷冻干燥法
制备
表征
抗肿瘤活性
HEPG2细胞
Glycyrrhetinic acid nanoparticle
Anti-solvent precipitation and freeze-drying method
Preparation
Characterization
Anti-tumor activity
HepG2 cells
