摘要
目的:制备聚苹果酸-聚乙二醇-叶酸(PMLA-PEG-FA)纳米共聚物,为构建多功能靶向药物转运系统提供前期工作。方法:配体叶酸(FA)通过α-羟基-ω-醛基聚乙二醇(HO-PEG-CHO)以腙键连接在经过水合肼修饰的聚苹果酸的主链上。核磁共振光谱表征纳米共聚物的结构,动态透析法研究腙键响应不同pH值的断键特性,监测不同pH值共聚物中叶酸的稳定性。并采用SM-CC-7721人体肝癌细胞测定该纳米共聚物的细胞毒性。结果:1、经核磁共振表征PMLA-PEG-FA共聚物合成完成。2、在pH5.5、pH6.5及pH7.4的PBS缓冲体系中,6h后配体叶酸累积释放率分别为88.1%,85.3%和41.6%。3、MTT实验证实PMLA-PEG-FA无毒性。结论:PMLA-PEG-FA有望成为智能靶向药物载体。
Objective： To prepare the folated-decorated poly （13-malic acid）-poly （ethylene glycol） nano-copolymers （abbreviated as PMLA-PEG-FA） which is to provide a new type of drug carrier for anticancer drug delivery system. Methods： The structure of this copolymer was confirmed by 1H-HMR. Moreover, the FA conjugation efficiency and FA release property were determined. The cytotoxicity was assessed by using human hepatocarcinoma SMMC-7721 cells as in vitro cell model. Results： 1. The copolymer was prepared successfully. 2. In vitro FA release from PMLA-PEG-FA conjugate occurred at a faster rate at acidic pH compared with neutral pH（7.4）. After 6h of incubation at pH 5.5, pH 6.5 and pH7.4 the released free FA was about 88.1%, 85.3% and 41.6%. Conclusion： PM- LA-PEG-FA nanocopolymer is expected to be used as an intelligent active-targeting drug carrier.
出处
《现代生物医学进展》
CAS
2012年第21期4019-4022,4061,共5页
Progress in Modern Biomedicine
基金
国家自然科学基金(30970788)
关键词
聚苹果酸
腙键
纳米共聚物
主动靶向
PH响应
Poly （13-malic acid）
Hydrazone bond
Nanocopolymer
Active targeting
pH response
