磁性紫杉醇-四氧化三铁-载药脂质体复合体微粒磁靶向脑内分布的实验研究  

Study on the targeted distribution of paclitaxel-loaded magnetic iron oxide/liposome nanoparticles in brain tissue

作　　者：闫润民[1] 梁超[1] 赵明[1] 张嘉靖[1] 易林华[1] 傅相平[1] 常津[2] 李安民[1] 

机构地区：[1]解放军总医院第一附属医院神经外科,北京100048 [2]天津大学材料科学与工程学院纳米生物技术研究所,天津300072

出　　处：《生物医学工程与临床》2011年第2期103-106,88,共4页Biomedical Engineering and Clinical Medicine

基　　金：国家自然科学基金资助项目(30772245)

摘　　要：目的探讨磁性紫杉醇-四氧化三铁-载药脂质体复合体微粒在磁场作用下在脑内的定向分布趋向。方法用壳聚糖、胆固醇、纳米级四氧化三铁、紫杉醇制成载药复合体微粒,通过体外透射电子显微镜和磁力计观察其形态和磁感应性。经尾静脉注入实验大鼠体内,头部一侧外加永磁磁场1 h。取大脑皮质,行普鲁士蓝染色,观察铁磁微粒在脑内的分布情况;高效液相色谱分析测定脑组织内紫杉醇含量。结果磁性紫杉醇-四氧化三铁-载药脂质体复合体微粒系统粒径15 nm左右,在外加磁场作用下可以定向积聚于靶区。普鲁士蓝染色显示实验组动物脑毛细血管外周和脑组织细胞内有铁微粒进入;高效液相色谱分析显示磁场靶区脑组织内紫杉醇浓度是对照组的5倍以上。结论磁性紫杉醇-四氧化三铁-载药脂质体复合体微粒是一种较理想的药物载体,具有良好的超顺磁响应性,在外加磁场驱动下可通过血-脑屏障定向分布于脑组织细胞间质并进入细胞内,显著提高靶区化学治疗药物浓度,提高抗肿瘤效应。Objective To investigate the targeted distribution of paclitaxel-loaded magnetic iron oxide drug/liposome nanoparticles in brain tissue under the magnetic field.Methods Chitosan,cholesterol,magnetic iron oxide nanoparticles and paclitaxel were mixed to prepare paclitaxel-loaded magnetic iron oxide/liposome nanoparticles.The morphological characteristic of the nanoparticles was observed by transmission electron microscopy（TEM） and the in vitro magnetic induction response was measured by magnetometer.The nanoparticles were injected into rat via caudal vein and permanent magnetic field was placed on one side of the rat head for 1-hour.The distribution of ferromagnetic particles in brain was observed under microscope after Prussian blue staining and the paclitaxel content in brain tissue was analyzed by high-performance liquid chromatography.Results The diameter of paclitaxel loaded magnetic iron oxide/liposome nanoparticles was about 15 nm.The nanoparticles were accumulated in targeted region under external magnetic field.Prussian blue staining showed that magnetic iron oxide particles passed through capillary walls and entered the brain cells.The concentration of paclitaxel in targeted brain tissue was 5-time higher than that of the control group.Conclusion It is demonstrated that the paclitaxel loaded magnetic iron oxide/liposome nanoparticles are ideal drug carrier with super paramagnetic response characteristics.Driven by external magnetic field,they could pass through blood-brain barrier and enter intercellular substance and cells,which significantly increase the concentration of chemotherapeutics in targeted region and improve the anti-tumor effect.

关 键 词：紫杉醇 四氧化三铁 脂质体复合体 载药系统 磁靶向 化学药物疗法 

分 类 号：R944[医药卫生—药剂学]