超顺磁性紫杉醇纳米微粒对中枢神经系统肿瘤磁靶向药物化疗的实验研究

Study on magnetic targeted chemotherapy of superparamagnetic paclitaxel nanoparticles to central nervous system tumor

目的探讨超顺磁性紫杉醇纳米微粒在中枢神经系统肿瘤磁靶向药物化疗中的可行性。方法采用改性壳聚糖、四氧化三铁磁流体、胆固醇和紫杉醇制备超顺磁性紫杉醇纳米微粒,观察其超微结构和磁响应性。将制备的超顺磁性紫杉醇纳米微粒经尾静脉注入大鼠体内,头部置0.5T均匀磁场中,高效液相色谱法榆测不同处理组各观察时间点大鼠脑组织紫杉醇浓度,观察超顺磁性紫杉醇纳米微粒对血-脑屏障的通透性。结果磁滞曲线显示,制备的磁性紫杉醇纳米微粒具有超顺磁性。磁靶向组大鼠各观察时间点脑组织紫杉醇浓度均高于非磁靶向组和单纯药物组,组间差异具有统计学意义(均P<0.05),其靶区药物浓度较单纯药物组提高5～30倍,且可维持局部药物浓度>16h。光学显微镜观察显示,磁靶向导向下超顺磁性紫杉醇纳米微粒可沉积于大鼠脑皮质微血管,并透过血-脑屏障进入神经细胞。结论磁靶向导向下超顺磁性紫杉醇纳米微粒可有效提高脑组织内化疔药物浓度,并透过血-脑屏障,进入靶向神经细胞而发挥药物作用。

Objective To explore the feasibility of using paelitaxel （PTX） - loaded superparamagnetic nanoparticles for the treatment of glioma in magnetic targeted chemotherapy. Methods Superparamagnetic paclitaxel nanoparticles were made from modified chitosan, Fe3O4 ferromagnetic fluid, cholestorol and paclitaxel. They were tested with transmission electron microscope （TEM） and vibration specimen magnetometer to observe their morphology and magnetism. They were injected into rats through caudal vein and a 0.5T magnetic field was placed across the rats＇ head in magnetic targeting group. The paclitaxel concentration in rats＇ brain was tested. The distribution of superparamagnetic paclitaxel nanoparticles was stained by Prussion staining and observed by light microscope. Results The paclitaxel nanoparticles were superparamagnetic and elevated local drug concentration significantly in magnetic targeting group compared with non- magnetic targeting group and control group （P 〈 0.05, for all）. It enhanced the drug concentration for 5-30 times and prolonged the high drug concentraion for more than 16 hours. Microscopic observation found that superparamagnetic paclitaxel nanoparticles concentrated in cortex microvessels and entered neurons by penetrating the blood- brain barrier （BBB）. Conclusion Superparamagnetic paclitaxel nanoparticles may improve the local drug concentration in brain and enter neurons under magnetic targeted chemotherapy, and develop the drug action.