叶酸受体介导的负载紫杉醇纳米药物输送系统的制备

Preparation and Characterization of Folate Receptor-mediated Delivery of Paclitaxel Nanoparticle System

目的:构建靶向肿瘤组织的药物输送系统,是解决目前临床肿瘤化疗问题的有效途径之一。我们拟开展叶酸受体介导的负载紫杉醇纳米药物输送系统的制备及其表征。方法:以丁二酰化肝素为载体,通过碳二亚胺法将叶酸和丁二酰化肝素连接,制备肝素-叶酸偶联物,然后通过物理方法将紫杉醇包裹在肝素-叶酸偶联物中,在水溶性条件下体系自组装成肝素-叶酸-紫杉醇纳米粒。应用核磁共振氢谱(1H NMR),动态光散射(DLS)和扫描电子显微镜(SEM)对构建的纳米药物结构进行表征,同时观测其在水溶性条件下的自组装行为。结果:成功制备了肝素-叶酸-紫杉醇纳米药物输送系统,检测表明药物系统带有8.5%(w/w)的叶酸并负载9.6%(w/w)的药物,SEM检测表明形成了球状的纳米颗粒,DLS表明粒子的粒径在了86 nm左右。结论:我们成功制备了叶酸受体介导的负载紫杉醇的纳米药物输送系统,在进一步开展的生物活性的检测中,希望通过叶酸受体的靶向作用,引导药物定向分布在肿瘤组织,从而提高化疗药物的治疗效果同时降低其对正常细胞的毒副作用,为开发新型靶向药物输送系统提供基础。

Objective： Fabrication of targeting drug delivery system has become an efficient method for improving specific accumulation of drug in tumor tissue and overcoming its adverse side effects.Herein,we prepared and characterized folate receptor-mediated delivery of paclitaxel nanoparticle system.Methods： We selected succinyl-heparin as carrier to conjugate with folate by EDC/ NHS,and then paclitaxel was entrapped into heparin-folate and formed a self-assembled heparin-folate-paclitaxel nanoparticle in aqueous solution.The structure of naoparticles was characterized by 1H NMR,and its morphology and size of were measured by scanning electron microscopy（SEM） and dynamic lighting scatter（DLS）,respectively.Results： We successfully prepared heparin-folate-paclitaxel nanoparticle system.It was shown that the weight percentage of folate and paclitaxel was about 8.5 % and 9.6 % using UV analysis and HPLC.Our results showed that the morphology of nanoparticles was approximately spherical shape as measured by SEM and the size of nanoparticles was about 86 nm determined by DLS.Conclusion： We fabricated folate receptor mediated-delivery of paclitaxel nanoparticle system which promoted us to further investigate its biological activities.The strategy on targeting nanoparticle drug delivery system was expected to be a promising approach allowing for increasing specificity in tumor and improving chemotherapeutic efficiency.