负载紫杉醇的双配体纳米药物输送系统的制备

Preparation and Characterization Heparin-based Nanoparticle with Dual Ligands to Deliver Paclitaxel

目的:带有叶酸和穿膜肽双配体的、负载紫杉醇纳米药物输送系统的制备及其表征。方法:以丁二酰化肝素为原料,利用碳二亚胺法偶联叶酸和穿膜肽,制备肝素-叶酸-穿膜肽偶联物,然后将紫杉醇包裹在肝素-叶酸-穿膜肽载体中,在水溶性条件下自组装成肝素-叶酸-穿膜肽-紫杉醇纳米粒子。本研究采用核磁共振氢谱(1H NMR),动态光散射(DLS)和透射电子显微镜(TEM)对自组装的纳米粒子进行表征,观测其在水溶性条件下的自组装行为。结果:成功构建了肝素-叶酸-穿膜肽-紫杉醇纳米粒子,检测表明纳米粒子含有8.5%的叶酸和5.5%穿膜肽并负载8.3%紫杉醇(w/w),TEM和DLS检测表明形成了不规则的球形纳米颗粒,粒径为78nm左右。结论:我们成功制备了带有双配体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和穿膜肽穿膜作用,提高药物在靶细胞的聚集,进一步增强药物输送系统的治疗作用,为开发新型、高效药物输送系统提供基础。

Objective.. Preparation and characterization of heparin-based nanoparticles delivery of paclitax- el composed of folate and Tat dual ligands. Methods： Succinyl-heparin was used to conjugate with folate and Tat by EDC/NHS, and then paclitaxel was entrapped into heparin-folate-Tat carrier and formed a self-assem- bled heparin-folate-Tat-paclitaxel nanoparticle in aqueous solution. The naoparticles was characterized by 1H NMR, transmission electron microscopy （TEM） and dynamic lighting scatter （DLS）, respectively. Results. The heparin-folate-Tat-paclitaxel nanoparticles were successfully prepared. The weight percentage of folate, Tat and paclitaxel was about 8. 5 ~, 5.5 and 8. 4 %, respectively. The morphology of nanoparticles was ap- proximately spherical shape as measured by TEM and the size of nanoparticles was about 78 nm as deter- mined by DLS. Conclusions. We fabricated heparin-based nanoparticles with dual ligands to deliver paclitaxel which promoted us to further investigate its biological activities. The strategy on nanomedicine with dual lig- ands was expected to enhance the cellular uptake of drug thereby improving promising its chemotherapeutic efficiency. The nanoparticle system could be used as a promising cancer cell specific delivery system for fur- ther investigation.