摘要
制备穿心莲内酯（andrographolide,AP）-甘草酸（glycyrrhizic acid,GA）纳米胶束,以增强穿心莲内酯的溶解性和抗肿瘤效果。首先,以穿心莲内酯为模型药物,甘草酸为载体,制备穿心莲内酯-甘草酸胶束[（AP-GA）-PMs],以胶束的粒径、包封率、载药量为指标,考察不同制备方法及载药比对所制备胶束的影响,筛选出最优处方及制备工艺;对最优处方工艺制备的（AP-GA）-PMs的制剂学性质及对肝癌细胞（HepG2）增殖的抑制作用进行评价。结果表明,最优处方工艺所制备的（AP-GA）-PMs澄清透明呈球形粒径为（127.11±1.38）nm,Zeta电位为（-24.01±0.55）mV,包封率为（92.01±4.02）%,载药量为（51.44±1.24）%,4℃储存30 d内稳定,体外释放缓慢、稳定较高。体外细胞毒性结果显示,GA对AP具有协同抗肿瘤作用,同时（AP-GA）-PMs（IC50=19.25 mg·L^-1）显著增加了AP（IC50=122.40 mg·L^-1）对HepG2细胞毒性（P〈0.01）。综上,甘草酸作为载体所制备的（AP-GA）-PMs,粒径小,载药量大,稳定性高,并显著提高了AP的抗肿瘤活性。
This study aimed to prepare andrographolide（AP）-loaded glycyrrhizic acid（GA） micelles（AP-GA）-PMs to enhance the solubility and anti-tumor effect of andrographolide.Firstly,andrographolide（AP） was used as the model drug and glycyrrhizic acid（GA） as carriers to prepare（AP-GA）-PMs.Then the preparation methods and the ratios of drug and carrier were screened and optimized based on particle size,encapsulation efficiency（EE） and loading capacity of micelles.Finally,the pharmaceutical characters and the inhibition rate on HepG2 cells were evaluated on the（AP-GA）-PMs prepared by optimal process.The results showed that the prepared micelles under the optimal process had a nanosize of（127.11±1.38） nm,zeta potential of（-24.01±0.55） mV,the entrapment efficiency rate of（92.01±4.02） %,the drug loading rate of（51.44±1.24） % and high storage stability at 4℃ in 30 d,with slow but highly stable in vitro release.Moreover,（AP-GA）-PMs with the IC50 value of 19.25 mg·L^-1 had a more synergistic and better anti-tumor effect in comparison with AP（IC50=122.40 mg·L^-1） on HepG2 cells（P〈0.01）.In conclusion,the（AP-GA）-PMs prepared with glycyrrhizic acid as a carrier had a small particle size,large drug loading capacity,and high stability,and could significantly improve the anti-tumor effects of AP.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2018年第1期79-85,共7页
China Journal of Chinese Materia Medica
基金
国家自然科学基金项目(81503262)
关键词
穿心莲内酯
甘草酸
纳米胶束
薄膜分散法
载药量
协同抗肿瘤
andrographolide
glycyrrhizic acid
micelles
film-thin dispersion method
loading efficiency
synergistic anti-tumor effects
