Tian Hua Yu, Deng Chao, Lin Hao, Sun Jingru, Deng Mingxiao, Chen Xuesi, Jing Xiabin
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, ChangChun, Jilin 130022, China.
Biomaterials. 2005 Jul;26(20):4209-17. doi: 10.1016/j.biomaterials.2004.11.002.
A novel amphiphilic biodegradable cationic hyperbranched poly(ethylene glycol)-polyethylenimine-poly(gamma-benzyl L-glutamate) (PEG-PEI-PBLG) block copolymer was successfully synthesized by ring-opening polymerization (ROP) of N-carboxyanhydride of gamma-benzyl-L-glutamate (BLG-NCA) with PEG-PEI as a macroinitiator. PEG-PEI was firstly prepared by coupling of PEG and PEI using hexamethylene diisocyanate (HMDI). The structural properties of PEG-PEI-PBLG copolymers were confirmed by 1H NMR and GPC. The copolymers were found to be self-assembled in water with critical micelle concentration (CMC) in the range of 0.00368-0.0125 g/l and high hydrophobic micelle core. The micelle size and CMC obviously depended on the hydrophobic block content in the copolymer and the ionic state of the PEI block. The CMC decreased with the increase in the PBLG block content. The decrease of micelle size and the increase of CMC simultaneously occurred with the protonated degree of PEI block by addition of HCl solution. ESEM and Gel retardation assay showed that the cationic micelles had ability to encapsulate plasmid DNA. The copolymer has potential medical applications in drug and gene delivery.
以聚乙二醇 - 聚乙烯亚胺(PEG - PEI)为大分子引发剂,通过γ - 苄基 - L - 谷氨酸N - 羧酸酐(BLG - NCA)的开环聚合(ROP)反应,成功合成了一种新型两亲性可生物降解阳离子超支化聚(乙二醇) - 聚乙烯亚胺 - 聚(γ - 苄基 - L - 谷氨酸)(PEG - PEI - PBLG)嵌段共聚物。首先使用六亚甲基二异氰酸酯(HMDI)将PEG和PEI偶联制备PEG - PEI。通过1H NMR和GPC对PEG - PEI - PBLG共聚物的结构性质进行了确认。发现该共聚物在水中自组装,临界胶束浓度(CMC)在0.00368 - 0.0125 g/l范围内,且胶束核心具有高疏水性。胶束大小和CMC明显取决于共聚物中疏水嵌段的含量以及PEI嵌段的离子状态。CMC随PBLG嵌段含量的增加而降低。通过添加HCl溶液使PEI嵌段质子化时,胶束大小减小和CMC增加同时发生。环境扫描电子显微镜(ESEM)和凝胶阻滞试验表明,阳离子胶束具有包裹质粒DNA的能力。该共聚物在药物和基因递送方面具有潜在的医学应用价值。