【作者】 梅林； 宋存先； 金旭； 车永哲； 金喆； 孙洪范；

【Author】 MEI Lin1, SONG Cun-xian 1, JIN Xu1, CHE Yong-zhe 2, JIN Zhe3, SUN Hong-fan1* 1. Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, The Tianjin Key Laboratory of Biomaterial Research, Tian Jin 300192, China 2. Medical College of Nankai University, Tian Jin 300192, China 3. Department of Cardiology, Tianjin First Central Hospital, Tian Jin 300192, China

【机构】 中国医学科学院&中国协和医科大学生物医学工程研究所天津市生物医学材料重点实验室； 南开大学医学院； 天津市第一中心医院心内科；

【摘要】 目的制备表面修饰紫杉醇纳米微球并研究其在兔颈动脉损伤模型的抑制新生内膜增生的效果。方法采用超声乳化-溶剂挥发法制备载紫杉醇纳米微球,用物理吸附法对纳米微球进行表面修饰。对纳米微球进行表征,包封率和体外释放使用高效液相色谱仪进行分析。建立兔颈动脉损伤模型,在血管局部灌注不同浓度的修饰纳米粒。28天后,取出局部给药的颈动脉血管,进行HE染色和弹力纤维染色。结果制备成粒径300纳米左右、包封率80%以上且表面带正电荷的载紫杉醇纳米微球。体外药物释放呈三相释放。28天后,血管内局部灌注紫杉醇纳米悬液可有效抑制血管内皮增生,抑制效果随纳米粒悬液浓度的增加而提高。浓度达到30mg/ml时,可完全抑制血管内膜增生。结论血管内局部灌注正电荷修饰的紫杉醇纳米悬液可有效抑制血管内皮增生,抑制效果随纳米粒悬液浓度的增加而提高。更多还原

【Abstract】 Aim Paclitaxel has been shown to inhibit vascular smooth muscle cell migration and proliferation contributing to neointimal formation. This study tested whether novel paclitaxel-loaded nanopaticle through surface conjugation with DMAB can prevent neointimal formation in a rabbit carotid artery injury model. Methods Paclitaxel-loaded nanoparticle were formulated from oil–water emulsions using biodegradable poly(lactic acid–co-glycolic acid)(PLGA), and specific additives for surface conjugation after particle formation, to enhance arterial retention using didodecylmethylammoniumbromide (DMAB). The size and size distribution, surface morphology and surface charge of the paclitaxel-loaded nanoparticles were then investigated by laser light scattering, scanning electron microscope and zeta potential analyzer. The drug encapsulation efficiency (EE) and in vitro release profile were measured by high-performance liquid chromatography (HPLC). Rabbit carotid artery injury model was established to examine the inhibitory effects of this novel formulation on VSMC migration and proliferation. Results The obtained nanoparticles (NP) with a positive surface charge showed a spherical diameter ranging from 200 to 500 nm. The in vitro drug release profile showed a triphasic release pattern. 28 days later, morphometric analyses revealed that the inhibitory effect of intima proliferation is dose-dependent, and the 30 mg/ml nanoparticle concentration suspension could completely inhibit proliferation of intima. Conclusions Paclitaxel-loaded nanoparticles through surface conjugation with DMAB provide an effective means of inhibiting proliferative response to vascular injury in the rabbit. Thus, this novel formulationm may prevent human restenosis without significant toxicity.更多还原