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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: To construct a drug delivery system targeting tumor tissue is one of the effective ways to solve the current clinical tumor chemotherapy. We propose to develop and characterize the folate receptor-mediated delivery system of paclitaxel loaded nano-drug. Methods: Heparin-folic acid conjugates were prepared by the conjugation of folic acid and succinylated heparin via the carbodiimide method using succinyl-heparin as a carrier. Paclitaxel was then physically encapsulated in a heparin-folate conjugate , The system self-assembled into heparin-folate-paclitaxel nanoparticles under water-soluble conditions. The structure of the drug was characterized by 1H NMR, DLS and SEM. The self-assembly behavior of the drug was observed under water-soluble conditions. RESULTS: A heparin-folate-paclitaxel nanodrug delivery system was successfully prepared. The drug system was found to contain 8.5% (w / w) folic acid and loaded with 9.6% (w / w) of drug. SEM results showed that spherical nanoparticles Particles, DLS, indicate that the particle size is about 86 nm. CONCLUSION: We successfully prepared the folate receptor mediated paclitaxel-loaded nanomedicine delivery system. In the further study of biological activity, we hope to guide the drug to be oriented in the tumor tissue through the targeted effect of folate receptors and thus improve Therapeutic effects of chemotherapeutic drugs while reducing their toxic effects on normal cells provide a basis for the development of novel targeted drug delivery systems.