Biodegradable poly (ethylenimine) for plasmid DNA delivery
Biodegradable poly (ethylenimine) for plasmid DNA delivery
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DOI：
10.1016/s0168-3659(01)00547-8
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发表时间：
2002-04-23
影响因子：
10.8
通讯作者：
Kim, SW
中科院分区：
文献类型：
--
作者：
Ahn, CH;Chae, SY;Kim, SW
聚乙亚胺（PEI）是一种高效的基因载体，具有最高的阳离子电位。PEI的高转染效率及其细胞毒性在很大程度上取决于分子量。以低分子量PEI和亲水性聚乙二醇（PEG）为原料合成水溶性、生理条件下可降解的阳离子共聚物，用于质粒传递。亲水性PEG有望降低共聚物的毒性，改善PEI和DNA配合物的溶解度差，并有助于通过与PEI中的伯胺反应引入可降解键。考虑到转染效率和细胞毒性依赖于PEI的分子量，期望通过增加共聚物的分子量来提高转染效率，通过引入PEG并将共聚物降解为低分子量PEI来降低细胞毒性。仔细控制反应条件以制备水溶性共聚物。凝胶缓凝实验和齐势仪结果表明，共聚物/ psv - β -gal质粒的电荷比在0.8 ~ 1.0之间，复合物的平均粒径在129.8+/-0.9 ~ 151.8+/-3.4 nm之间，复合物完全中和。合成的共聚物体外转染效率比起始低分子量PEI提高了3倍，而细胞存活率保持在80%以上。(C) 2002 Elsevier Science B.V.版权所有
Poly(ethylenimine) (PEI) has been known as an efficient gene carrier with the highest cationic charge potential. High transfection efficiency of PEI, along with its cytotoxicity, strongly depends on the molecular weight. Synthesis of cationic copolymers derived from the low molecular weight of PEI and hydrophilic poly(ethylene glycol) (PEG), which are water soluble and degradable under physiological conditions, was investigated for plasmid delivery. Hydrophilic PEG is expected to reduce the toxicity of the copolymer, improve the poor solubility of the PEI and DNA complexes, and help to introduce degradable bonds by reaction with the primary amines in the PEI. Considering the dependence of transfection efficiency and cytotoxicity on the molecular weight of the PEI, high transfection efficiency is expected from an increased molecular weight of the copolymer and low cytotoxicity from the introduction of PEG and the degradation of the copolymer into low molecular weight PEIs. Reaction conditions were carefully controlled to produce water soluble copolymers. Results from a gel retardation assay and zetapotentiometer indicated that complete neutralization of the complexes was achieved at the charge ratios of copolymer/pSV-beta-gal plasmid from 0.8 to 1.0 with the mean particle size of the polyplexes ranging from 129.8+/-0.9 to 151.8+/-3.4 nm. In vitro transfection efficiency of the synthesized copolymer increased up to three times higher than that of starting low molecular weight PEI, while the cell viability was maintained over 80%. (C) 2002 Elsevier Science B.V. All rights reserved.