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  

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

作　　者：汤芊 史晓欣 贺冬秀[1] 熊润德 唐国涛[1] TANG Qian;SHI Xiaoxin;HE Dongxiu;XIONG Runde;TANG Guotao(Institute of Pharmacy and Pharmacology,University of South China,Hengyang,Hunan 421001,China)

机构地区：[1]南华大学药物药理研究所,湖南衡阳421001

出　　处：《南华大学学报（自然科学版）》2018年第3期90-96,共7页Journal of University of South China：Science and Technology

基　　金：湖南省教育厅创新平台开放基金项目(16K079;17K082)

摘　　要：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.Drug delivery nanosystem FA-PAMAM-FUA was prepared through covalently coupling the amino group of polyamide amine（ PAMAM） with the carboxylic group of folicacid（ FA） and 5-fluorouracil acetic acid（ FUA）,respectively. The optimized mole ratio of FA ∶ PAMAM ∶ FUA was 10 ∶ 1 ∶ 450 and the optimized p H 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-PAMAMFUA 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.

关 键 词：5-氟尿嘧啶 叶酸 聚酰胺-胺 缓释 MCF-7 

分 类 号：R318[医药卫生—生物医学工程]