热驱动自组装白蛋白纳米粒的制备及体外评价  

Preparation and in vitro evaluation of albumin nanoparticles produced by thermal driven self-assembly

作　　者：李芳[1,2] 姜力群 辛俊勃[2] 郑春丽[1] 朱家壁[1] 刘建平[1] 

机构地区：[1]中国药科大学药剂学教研室,南京210009 [2]盐城卫生职业技术学院药学院,盐城224005 [3]徐州医科大学药学院,徐州221004

出　　处：《中国药科大学学报》2016年第3期303-310,共8页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.81402878);江苏省普通高校研究生科研创新计划项目(No.CXZZ13_0327)~~

摘　　要：探讨热驱动自组装白蛋白纳米粒的制备方法,并对其形成机制、细胞摄取、细胞摄取动力学与降解动力学等进行考察。通过测定巯基、氨基与羧基的浓度揭示白蛋白纳米粒的形成机制。采用CCK-8法检测纳米粒的细胞毒性,通过倒置荧光显微镜观察纳米粒的摄取行为,采用荧光共振能量转移(FRET)法测定白蛋白纳米粒在细胞内的摄取与降解动力学,并以紫杉醇为模型药物考察其对疏水性药物的包载能力。结果表明,热驱动自组装法制得的白蛋白纳米粒依靠分子间二硫键与酰胺键而稳定,安全无毒,易于被肿瘤细胞摄取并在胞内降解。载药实验结果显示,该纳米粒对紫杉醇有较高的包载。因此,热驱动自组装法绿色环保、操作简便,制得的白蛋白纳米粒可作为抗肿瘤药物传递的新平台。The aim of this study was to prepare albumin nanoparticles by thermal driven self-assembly, and to investigate the formation mechanism, cellular uptake, the kinetics of cellular uptake and intracellular degradation, etc. By measuring the concentrations of thiol, amino and carboxyl groups, the formation mechanism of albumin nanoparticles was revealed. CCK-8 assay was performed to detect the cytotoxicity; inverted fluorescence microscope was used to observe the cellular uptake of the nanoparticles; while the fluorescence resonance energy transfer（FRET）method was applied to investigate the cellular uptake and intracellular degradation kinetics. The drug-loading capacity was investigated using paclitaxel（PTX）as the model drug. The results showed that the albumin nanoparticles produced by thermal driven self-assembly were safe, nontoxic, biodegradable and stabilized by intermolecular disulfide and amide bonds. The drug-loading study indicates that PTX can be highly encapsulated in the nanoparticles. Hence, thermal driven self-assembly method is green and easy to operate, and the albumin nanoparticles can be applied as a new delivery platform for anticancer drugs.

关 键 词：热驱动自组装 白蛋白纳米粒 紫杉醇 制备 形成机制 胞内降解动力学 

分 类 号：R943[医药卫生—药剂学]