磷酰N-十四酰吉西他滨脂质衍生物自组装体的制备、性质和抗肿瘤作用

目的 制备磷酰N-十四酰吉西他滨（CPTG）脂质衍生物自组装体并考察其性质和抗肿瘤作用.方法 合成CPTG脂质衍生物,用Langmuir膜天平考察该前药分子成膜性,用注入法制备自组装体,通过透射电镜观察形态,用纳米激光粒度仪测定粒径,用HepG2细胞模型和荷瘤小鼠模型考察其药效学.结果 以吉西他滨为原料合成得到CPTG.水/空气界面上的表面压-分子面积曲线显示前药分子呈两亲性,成膜性好.前药自组装体呈囊泡状,粒径为93.52 nm,Zeta电位为-31mV.前药自组装体与原药吉西他滨相比,对HepG2细胞和H22实体瘤抑制作用显著.结论 CPTG脂质衍生物自组装体为肝癌靶向治疗提供了一种新方法.

Preparation,properties and anti-tumor effect of the self-assemblies of a phosphoryl N-tetradecanoyl gemcitabine derivative

Objective To prepare the self-assemblies of a phosphoryl N-tetradecanoyl gemcitabine （CPTG） derivative and evaluate the properties and anti-tumor effect. Methods CPTG derivative was synthesized. The prodrug membrane was investigated using a Langmuir trough. The self-assembly was prepared using the injection method. The morphology of self-assemblies was observed by a transmission electron microscope. The particle distribution was measured by a dynamic light scattering instrument. The pharmaco- dynamic effect was evaluated on HepG2 cells and tumor-bearing mice. Results The prodrug was synthesized with gemcitabine as the raw material. The surface pressure-molecular area （T-a） curves at the air/water interface indicated that the prodrug was amphiphilic and formed the stable monolayer. The self-assemblies formed the vesicles with the mean size of 93.52 nm and the Zeta potential of - 31 mV. The inhibitory effects of self-assemblies were significantly higher than those of gemcitabine on the models of HepG2 cells and the tumor-bearing mice. Conclusion The self-assemblies of the amphiphilic prodrug of gemcitabine might be a promising novel nano- medicine for targeted therapy of liver cancer.