携Fe_3O_4靶向血栓聚乳酸-羟基乙酸微球的制备及体外MR成像研究  

Preparation and in vitro MR imaging of Fe_3O_4-loaded PLGA microparticles targeting thrombus

作　　者：周君[1] 张瑜[1] 郭大静[1] 熬梦[2] 郑元义[2] 王志刚[2] 

机构地区：[1]重庆医科大学附属第二医院放射科,重庆400010 [2]重庆医科大学超声影像学研究所,重庆400010

出　　处：《第三军医大学学报》2013年第19期2033-2036,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81171332)~~

摘　　要：目的制备携Fe3O4靶向血栓的聚乳酸-羟基乙酸(poly lactic-co-glycolic acid,PLGA)微球,探讨其理化性质并在MR监测下观测其对体外血栓的靶向能力。方法以PLGA为载体,通过双乳化溶剂挥发法及碳二亚胺法制备携带MR造影剂Fe3O4及表面修饰血栓亲和性短肽精氨酸-甘氨酸-天冬氨酸-丝氨酸(Arg-Gly-Asp-Ser,RGDS)的PLGA微球(RGDS-Fe3O4-PLGA微球),对其理化性质进行表征,通过体外靶向血栓实验探究其对血栓的靶向能力,并评价其MR显影效果。结果成功制备了RGDS-Fe3O4-PLGA微球,激光粒径仪测得微球的粒径为(1 105±83)nm,其形态规则,大小均匀,呈球形,分散性好,火焰原子吸收光谱法测得Fe3O4携带率为43.6%,流式细胞仪检测RGDS的连接率为23.57%。在MR监测下,体外血栓寻靶实验证实该微球可有效靶向血栓并明显降低血栓周边T2信号。结论本实验制得的RGDSFe3O4-PLGA微球对体外血栓有良好的亲和性,MR对比增强效果好。Objective To prepare Fe304-loaded thrombus-targeting poly lactic-co-glycolic acid （PLGA） microparticles, and to investigate its related characteristics and targeting ability to thrombus in vitro by MRI. Methods PLGA was employed as the core of microparticles of drug carriers. Fe304-1oaded PLGA microparticles were first prepared through double emulsion solvent evaporation technique and the ligands Arg- Gly-Asp-Ser （RGDS） were further eovalently bound to the surface of microparticles via carbodiimide-mediated amide bond formation. The physical and chemical properties of RGDS-FeaO4-PLGA microparticles were measured, and their feasibility and efficacy of targeting thrombus were estimated by in vitro experiment. MR images of the microparticles were observed with a 3.0 T clinical MR scanner. Results The RGDS-Fe304- PLGA microparticles were spherical in shape with a mean diameter of 1 105 ±83 nm, and had neither aggrega- tion nor adhesion tendencies. The carrier rate of Fe3 04 was 43.6% through atomic absorption spectrometer, and the conjugate rate of RGDS was detected as 23.57% by flow cytometry. Pathological section confirmed that the microparticles specifically accumulated in the edge of thrombus. MR scanning demonstrated the microparticlcs effectively targeted thrombus and significantly decreased T2 signal on the edge of the thrombus. Gonclusion Our prepared RGDS-Fe3 O4-PLGA microparticles have good affinity to thrombus and exhibit contrast-enhanced effect in in vitro MI images.

关 键 词：氧化铁 PLGA 血栓 微球 RGDS 

分 类 号：R445.2[医药卫生—影像医学与核医学] R981[医药卫生—诊断学]