同源细胞膜包载多西他赛长循环脂质体的制备及体外评价  

Preparation and in vitro Evaluation of Docetaxel Long-circulating Liposomes Encapsulated by Homologous Cell Membranes

作　　者：解雅茹 王冠茹 孙考祥[1] XIE Yaru;Wang Guanru;Sun Kaoxiang(School of Pharmaceutical Sciences,Yantai University,Yantai 264005;Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203)

机构地区：[1]烟台大学药学院,山东烟台264005 [2]中国科学院上海药物研究所药物制剂研究中心,上海201203

出　　处：《中国医药工业杂志》2021年第10期1329-1336,共8页Chinese Journal of Pharmaceuticals

摘　　要：以氢化大豆磷脂酰胆碱、二硬脂酰磷脂酰乙醇胺-聚乙二醇2000及胆固醇为载体,采用薄膜分散法制备了多西他赛长循环脂质体(lip-DTX)。在此基础上,采用共挤出法制备小鼠乳腺癌(4T1)细胞膜包裹的多西他赛长循环脂质体(4T1/lip-DTX)。透射电镜观察到所制得的lip-DTX和4T1/lip-DTX形态圆整;粒度分析仪测得其粒径为(149.6±0.1)和(126.7±0.6)nm,ζ电位为(–40.5±2.1)和(–6.3±1.2)mV;超滤法测得包封率为(72.4±0.3)%和(74.1±0.2)%,载药量为(3.0±0.1)%和(2.5±0.5)%。二者在4℃条件下4 d内粒径和包封率均保持稳定。体外释放试验结果显示,lip-DTX释放缓慢,12 h时累积释放率为(69.5±0.4)%,而4T1/lip-DTX释放更缓慢,8 h累积释放率为(22.2±0.3)%。细胞摄取试验显示,小鼠单核巨噬(RAW 264.7)细胞对lip-DTX的摄取是4T1/lip-DTX的1.4倍(P<0.01),4T1细胞对4T1/lip-DTX的摄取是lip-DTX的1.5倍(P<0.001),提示4T1/lip-DTX具有长循环和靶向持性。4T1细胞毒性试验显示,lip-DTX及4T1/lip-DTX对4T1细胞的IC50值为7.6和1.5μg/ml,提示4T1/lip-DTX能增加药物的抗肿瘤效果。Using hydrogenated soybean phosphotidylcholine,distearoylphosphatidylethanolamine-polyethylene glycol 2000 and cholesterol as carriers,long-circulating liposomes of docetaxel(lip-DTX)were prepared by thin-film dispersion.On this basis,mouse 4T1 breast cancer cell membrane-encapsulated docetaxel long-circulating liposomes(4T1/lip-DTX)were prepared by co-extrusion.The morphologies of lip-DTX and 4T1/lip-DTX pictured by TEM were round.The particle size and zeta potential for lip-DTX and 4T1/lip-DTX measured by the analyzer were(149.6±0.1)and(126.7±0.6)nm,(–40.5±2.1)and(–6.3±1.2)mV,respectively.The encapsulation efficiencies measured by ultrafiltration were(72.4±0.3)%and(74.1±0.2)%for lip-DTX and 4T1/lip-DTX,while the drug loading were(3.0±0.1)%and(2.5±0.5)%.No significant changes were observed in particle size and encapsulation efficiency of lip-DTX and 4T1/lip-DTX stored at 4℃for 4 days.The results of in vitro release test showed that the cumulative amount at 12 h of lip-DTX was(69.5±0.4)%.While the cumulative amount at 8 h of 4T1/lip-DTX was(22.2±0.3)%,showing a slower release rate compared to lip-DTX.The cell uptake test showed that the uptake of lip-DTX by mouse monocyte macrophage cell line RAW 264.7 was 1.4 times that of 4T1/lip-DTX(P<0.01),and the uptake of 4T1/lip-DTX by 4T1 cells was 1.5 times that of lip-DTX(P<0.001),indicating the long circulation and targeting properties of 4T1/lip-DTX.The in vitro cytotoxicity test showed that the IC_(50) values of lip-DTX and 4T1/lip-DTX against 4T1 cells were 7.6 and 1.5μg/ml,which indicated that 4T1/lip-DTX could increase the antitumor efficacy of docetaxel.

关 键 词：同源细胞膜 多西他赛 长循环脂质体 仿生制剂 体外评价 

分 类 号：R944.9[医药卫生—药剂学]