介入性心血管内药物和基因纳米控释体系  

Interventional Delivery of Nanoparticles for Intravascular Site-specific Drug and Gene Therapy

作　　者：宋存先[1] 杨菁[1] 孙洪范[1] 冷希岗[1] 朱文玲[2] 曾勇[2] 管珩[2] 李拥军[2] 

机构地区：[1]中国协和医科大学,中国医学科学院生物医学工程研究所,天津300192 [2]中国协和医科大学北京协和医院,北京100730

出　　处：《纳米科技》2005年第5期13-17,共5页

基　　金：国家自然科学基金项目（39870196,50473059）;博士点基金（20030023004）

摘　　要：通过介入导管将药物和基因载运到血管内病灶部位，并在血管组织中长期释放。以生物可降解聚合物PLGA为基材，采用超声乳化／溶剂挥发法分别制备包载药物和基因的纳米粒子，对纳米粒子进行了表面修饰提高血管吸收性；用载反义MCP-1基因的纳米粒子转染平滑肌细胞，对平滑肌细胞基因组DNA进行PCR扩增；用兔髂总动脉和颈总动脉血管损伤模型进行灌注实验。体外释放实验表明均具有缓慢释放作用，凝胶电泳实验证明基因的结构未遭破坏。说明纳米粒子是非常理想的血管内导向定位药物和基因控释的载体。The objective of this paper is to develop a nanometer-sized drug release system which can achieve catheter-based intra-vascular site-specific delivery of drugs and genes, A ultrasound-emulsion/solvent-evaporation technique was employed to make the nanoparticles （NPs） using a biodegradable polymer PLGA as matrix material. The NPs were surface modified to enhance absorbability to the vascular wall, NPs which containing anti-MCP-1 gene was tested in vitro and cell tranfection, and was detected through PCR proliferation. NPs were tested in vivo by single infusion after balloon injury in the rabbit iliac and carotid models. In vitro drug release evaluation showed a sustained controlled release. The biological function of encapsulated gene was intact. The anti-MCP-1 NPs induced great cell transfection as determined by PCR and electrophoresis. Infusion of antisense MCP-1 gene nanoparticles in rabbit balloon injury model, can significantly inhibit intimal hyperplasia. In conclusion, Nanoparticle is a potential intravascular drug delivery preparation.

关 键 词：纳米粒子 药物控释 血管再狭窄 基因治疗 

分 类 号：R-33[医药卫生]