白蛋白修饰的仿脂蛋白载体的肿瘤靶向性研究  

Tumor targeted apolipoprotein carriers modified by albumin

作　　者：周凯 李瑾 韩蒙蒙 王倩倩 蒋雯 高巾媛 汤道权 ZHOU Kai;LI Jin;HAN Meng-meng;WANG Qian-qian;JIANG Wen;GAO Jin-yuan;TANG Dao-quan(School of Pharmacy,Jiangsu Provincial New Drug and Clinical Pharmacy Key Laboratory Xuzhou Medical University,XuZhou 221004,China)

机构地区：[1]徐州医科大学药学院江苏省新药研究与临床药学重点实验室,徐州221004

出　　处：《国际药学研究杂志》2018年第3期198-204,共7页Journal of International Pharmaceutical Research

基　　金：国家自然科学基金资助项目(81502997)

摘　　要：目的构建肿瘤靶向性好、生物安全性高的重组高密度脂蛋白载体。方法参照盘状高密度脂蛋白的结构,以相同的脂质成分和比例采用薄膜分散法制备脂核,选择白蛋白代替载脂蛋白AI孵育包裹于脂核周围形成脂蛋白载体;并对其微观形态、粒径、Zeta电位、紫杉醇于载体中的包封率和释药特性、肿瘤细胞摄取、小动物活体成像和生物安全性进行考察。结果重组脂蛋白载体粒径为(228.3±3.5)nm,Zeta电位为(-27.3±1.9)m V,包封率为(85.6±0.6)%,呈现明显的药物缓释特征;Hep G2细胞对重组脂蛋白的摄取量明显高于药物溶液组及LO2细胞;孵育白蛋白的载体在小鼠肿瘤部位可长时间、特异性蓄积,具有良好的肿瘤组织靶向性;细胞毒性和溶血性实验显示,重组脂蛋白载体具有良好的生物安全性。结论采用本实验方法制备的紫杉醇重组脂蛋白载体具有良好的肿瘤靶向特性和生物安全性,有望成为紫杉醇的新型靶向输送制剂。Objective To construct a recombinant high density lipoprotein carrier with good tumor targeting property and high biological safety. Methods Referring to the structure of the disc-high density lipoprotein（HDL）,lipid cores were prepared using the thin-film dispersion method with the same lipid composition and ratio. Instead of apolipoprotein AI,albumin was incubated to form lipoprotein carriers around the lipid core. The microscopic morphology,particle size,Zeta potential,encapsulation efficiency and drug release characteristics of paclitaxel in the carrier,uptake of tumor cells,the whole-body imaging of small animals and biological safety were investigated. Results The size of recombinant lipoprotein carrier was（228.3±3.5）nm,the Zeta potential was（-27.3±1.9）mV,and the encapsulation efficiency was（85.6±0.6）%. The uptake of recombinant lipoprotein by Hep G2 cells was significantly higher than that of the drug solution group and than LO2 cells. The albumin-incubated carriers tended to accumulate in the tumor site specifically for a long time and had good tumor targeting. Cytotoxicity test and hemolytic test showed that the recombinant lipoprotein carrier had good biosafety. Conclusion The recombinant lipoprotein carrier loading paclitaxel was endowed with excellent tumor targeting and biological safety and expected to serve as a novel targeting preparation.

关 键 词：脂蛋白 白蛋白 紫杉醇 肿瘤靶向性 生物安全性 

分 类 号：R944.9[医药卫生—药剂学]