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首页> 外文期刊>Polymers for advanced technologies >Design of polycationic micelles by self-assembly of polyethyleneimine functionalized oligo[(epsilon-caprolactone)-co-glycolide] ABA block copolymers
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Design of polycationic micelles by self-assembly of polyethyleneimine functionalized oligo[(epsilon-caprolactone)-co-glycolide] ABA block copolymers

机译：聚乙烯亚胺官能化寡核苷酸的自组装络合胶束的设计[（ε-己内酮）-CO-乙醇酸 - 乙酰甲醚] ABA嵌段共聚物

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摘要

Cationic polymeric micelles are of interest as delivery materials for nucleotides allowing condensation and transport of anionic macromolecules and enabling the reduction of cytotoxicity of polyethyleneimine, the current standard of vectors for non-viral nucleic acid delivery. In addition, micelles based on a degradable core would be capable to degrade hydrolytically and release their payload, which should preferably occur after uptake in early endosomes providing a pH of 5.5. We explored whether degradable and amphiphilic ABA block copolymers from hyperbranched polyethyleneimine A blocks and B blocks based on hydrophobic oligoesters (CG) can be created, which can degrade in a pH range relevant for the early endosomes. CG was synthesized by ring-opening polymerization of epsilon-caprolactone and diglycolide. Polycationic micelles with particle sizes between 19 +/- 1 and 43 +/- 2nm were obtained by self-assembly of the ABA block copolymers with different chain lengths of B blocks and/or co-assembly with a diblock copolymer from poly(ethylene glycol) (PEG) functionalized CG oligoester in phosphate-buffered saline solution. Mixed micelles containing PEG-CG showed a decreased zeta potential, suggesting a shielding by dangling PEG chains at the micelle surfaces. Sizes of cationic micelles were stable at pH=7.4 over the studied time period of 2weeks at 37 degrees C. The hydrolytic degradation was controlled by the composition of the CG core and was accelerated when the pH was decreased to 5.5 as detected by increasing micelle sizes. In this way, the polycationic micelles may act as an on-demand delivery system of condensed macromolecules. Copyright (c) 2016 John Wiley & Sons, Ltd.
机译：阳离子聚合物胶束对于允许阴离子大分子的缩合和转运并能够降低聚乙烯亚胺的细胞毒性的核苷酸，目前的非病毒核酸输送的载体标准。另外，基于可降解芯的胶束将能够水解地降解并释放其有效载荷，其应优选在提前底物中的摄取后发生的有效载荷，其pH为5.5。我们探讨了来自超支化聚乙烯亚胺的可降解和两亲性ABA嵌段共聚物，可以产生基于疏水性寡酯（CG）的嵌段和B嵌段，这可以在对早期内胚胎相关的pH范围内降解。通过ε-己内酯和二糖苷的开环聚合来合成CG。通过与来自聚二嵌段共聚物的不同链长的ABA嵌段共聚物的自组装和/或共聚物，通过来自聚（乙二醇的二嵌段共聚物，通过与聚（乙二醇的二嵌段共聚物（乙二醇）的（乙二醇）自组装和/或共聚物的粒子尺寸的聚溶解胶束获得。 ）（PEG）在磷酸盐缓冲盐水溶液中官能化CG寡核苷酸酯。含有PEG-CG的混合胶束显示出降低的Zeta电位，表明通过在胶束表面悬挂PEG链的屏蔽。阳离子胶束的尺寸在37摄氏度的研究时间为2周的时间周期下稳定。通过Cg核的组成来控制水解降解，并且如通过增加胶束尺寸检测到的pH值为5.5时加速。以这种方式，聚阳离子胶束可以用作浓缩大分子的按需输送系统。版权所有（c）2016 John Wiley＆Sons，Ltd。

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