摘要
目的制备藤黄酸脂质体(GA Lip),优化其处方并进行表征,考察GA Lip对4T1乳腺癌的抗肿瘤活性。方法采用薄膜分散法制备GA Lip,通过高效液相色谱(HPLC)法对藤黄酸(GA)含量测定进行方法学考察;以粒径和多分散系数为主要指标优化GA Lip的药脂比和投药量;测定GA Lip包封率;采用透射扫描电镜(TEM)观察其形貌;采用四甲基偶氮唑盐比色(MTT)法检测GA及GA Lip对4T1细胞的增殖抑制活性;建立4T1荷瘤小鼠模型,对比游离GA与GA Lip的体内抗肿瘤效果。结果优化后的GA Lip药脂比为1∶5,投药量为8 mg,包封率为(89.15±0.12)%,呈大小均一的椭圆形;GA及GA Lip对4T1细胞48 h的IC50分别为0.635μmol/L和0.294μmol/L;与游离GA组比较,GA Lip组小鼠肿瘤体积及重量更小。结论优化后的GA Lip稳定性较好,包封率高,与游离GA相比,GA Lip抗肿瘤活性更好,药效作用有所增强。
Objective To prepare liposomes of gambogic acid(GA Lip),optimize its prescription and characterize it to investigate the anti-tumor activity of GA Lip against 4T1 breast cancer.Methods The GA Lip was prepared by the thin-film dispersion method.The methodological investigation was carried out by highperformance liquid chromatography(HPLC)for the determination of garcinolic acid(GA)content.The particle size and dispersion coefficient were used as the main indicators to optimize the drug-to-lipid ratio and dosage of GA Lip.The encapsulation rate of GA Lip was determined and the morphology was observed using a transmission electron microscope(TEM).The proliferation-inhibitory activity of GA and GA Lip on 4T1 cells was measured using the 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)method.A 4T1 tumorbearing mouse model was established to compare the in-vivo anti-tumor effects of free GA with those of GA Lip.Results The optimized GA Lip had a lipid ratio of 1:5,a dosage of 8 mg and an encapsulation rate of(89.15±0.12)%in a uniformly sized oval shape.The IC50 of GA and GA Lip on 4T1 cells at 48 hours were 0.635μmol/L and 0.294μmol/L,respectively.Compared to the free GA group,the GA Lip group mice had smaller tumor volumes and weights.Conclusion The optimized GA Lip is more stable and has a high encapsulation rate.Compared to free GA,GA Lip has better anti-tumor activity and enhanced pharmacodynamic effects.
作者
李娇娇
王茹静
马菁
雷以珵
石三军
LI Jiaojiao;WANG Rujing;MA Jing;LEI Yicheng;SHI Sanjun(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Sichuan,Chengdu 611137,China)
出处
《中国医药科学》
2023年第19期74-77,127,共5页
China Medicine And Pharmacy
关键词
藤黄酸
脂质体
薄膜分散法
抗肿瘤活性
Gambogic acid
Liposomes
Thin-film dispersion method
Anti-tu mor activity
