Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
J Colloid Interface Sci. 2011 Feb 1;354(1):202-9. doi: 10.1016/j.jcis.2010.10.054. Epub 2010 Oct 28.
In this paper, folate conjugated poly(ε-caprolactone-co-4-maleate-ε-caprolactone) (P(CL-co-MCL)-folate) was prepared by a carbodiimide coupling reaction, i.e., the vitamin folic acid (FA) was covalently linked to the main chain of the maleate-functionalized polymer, poly(ε-caprolactone-co-4-maleate-ε-caprolactone) (P(CL-co-MCL)). Then the 5-Fluorouracil (5-FU) loaded nanoparticles of P(CL-co-MCL)-folate were achieved by solvent-evaporation method. Their properties were extensively studied by dynamic light scattering (DLS) and scan electron microscopy (SEM). DLS and SEM showed that the nanoparticles were in a well-defined spherical shape with a uniform size distribution. We also investigated the entrapment and in vitro release behavior, which indicated that the release speed of 5-FU could be well controlled and the release half-life period could reach 16.86h, which was 26.4 times longer than that of pure 5-FU. The in vitro targeting test displayed that the 5-FU loaded P(CL-co-MCL)-folate nanoparticles exhibited an enhanced cell inhibition because folate targeting increased the concentration of 5-FU loaded P(CL-co-MCL)-folate nanoparticles in the tumor cells with folate receptor overexpressed. Meanwhile, the tumor inhibition of 5-FU loaded P(CL-co-MCL)-folate nanoparticles was much higher than that of pure 5-FU and that of 5-FU loaded P(CL-co-MCL) nanoparticles. Therefore, P(CL-co-MCL)-folate nanoparticles would be highly beneficial for biomedical and pharmaceutical applications.
本文通过碳二亚胺偶联反应制备了叶酸偶联聚（ε-己内酯-co-4-马来酸酯-ε-己内酯）（P(CL-co-MCL)-叶酸），即将维生素叶酸（FA）共价连接到马来酸功能化聚合物的主链上，聚（ε-己内酯-co-4-马来酸酯-ε-己内酯）（P(CL-co-MCL)）。然后通过溶剂蒸发法制备了负载 5-氟尿嘧啶（5-FU）的 P(CL-co-MCL)-叶酸纳米粒子。通过动态光散射（DLS）和扫描电子显微镜（SEM）对其性能进行了广泛研究。DLS 和 SEM 表明，纳米粒子呈定义良好的球形，具有均匀的粒径分布。我们还研究了包封和体外释放行为，表明 5-FU 的释放速度可以得到很好的控制，释放半衰期可达 16.86h，是纯 5-FU 的 26.4 倍。体外靶向试验表明，负载 5-FU 的 P(CL-co-MCL)-叶酸纳米粒子由于叶酸靶向作用增加了叶酸受体过表达的肿瘤细胞中负载 5-FU 的 P(CL-co-MCL)-叶酸纳米粒子的浓度，从而表现出增强的细胞抑制作用。同时，负载 5-FU 的 P(CL-co-MCL)-叶酸纳米粒子的肿瘤抑制作用明显高于纯 5-FU 和负载 5-FU 的 P(CL-co-MCL)纳米粒子。因此，P(CL-co-MCL)-叶酸纳米粒子将非常有益于生物医学和制药应用。
