叶酸修饰聚酰胺-胺负载5-氟尿嘧啶纳米给药体系的制备及其体外性能研究

使用化学键键合的方式分别将叶酸(FA)和5-氟尿嘧啶-1-基乙酸(FUA)偶联于树状大分子聚酰胺-胺(PAMAM)制备纳米载药体系FA-PAMAM-FUA,并结合单因素分析法筛选出最佳制备条件为FA∶PAMAM∶FUA的物质的量的比为10∶1∶450,p H值为6.用紫外可见光谱、红外光谱和纳米粒度仪对FA-PAMAM-FUA的光学特性、粒径大小和体外释药性能进行了表征.结果表明:优化条件下制备的FAPAMAM-FUA粒径呈正态分布,平均粒径为90.28±20.00 nm,分散度为0.258±0.002(n=3),体系载药量达28.45%,FA-PAMAM-FUA给药体系对药物具有一定的p H敏感特性以及缓释功能.采用MTT法考察了5-Fu、FA-PAMAM-FUA对乳腺癌细胞MCF-7的增殖抑制作用,结果表明两者对MCF-7细胞的增殖具有明显地抑制作用,剂量依赖性强,随浓度的增高,FA-PAMAM-FUA对癌细胞增殖抑制作用较5-Fu明显增强.

Research on the Preparation and in Vitro Performance Evaluation of the Folic Acid Modified Polyamide-Amine Loaded 5-Fluorouracil Drug Delivery Nanosystem

Drug delivery nanosystem FA-PAMAM-FUA was prepared through covalently coupling the amino group of polyamide amine (PAMAM) with the carboxylic group of folic acid (FA) and 5-fluorouracil acetic acid(FUA),respectively.The optimized mole ratio of FAPAMAMFUA was 101450 and the optimized pH value was 6.The optical and release properties of as-prepared FA-PAMAM-FUA were characterized using UV-Visible spectra,infrared spectra,particle size and zeta potential.The average particle size and size dispersion of FA-PAMAM-FUA was 90.28±20.00 nm and 0.258±0.002(n=3),respectively.The drug-loading content of FA-PAMAM-FUA was 28.45%.The in vitro release profile of FUA from FA-PAMAM-FUA demonstrated a low and sustained release behaviour.The MTT assay was used to assess the proliferation inhibition of 5-Fu and FA-PAMAM-FUA on breast cancer cell MCF-7.The MTT results showed that both of them had a significant proliferation-inhibitory effect and a dose-dependent effect on the MCF-7 cells.And the results demonstrated that the resulting FA-PAMAM-FUA nanosystem were more potent in killing cancer cells as the spiked free 5-Fu or FA-PAMAM-FUA concentration were increased,compared to free 5-Fu.