Blood compatibility of novel water soluble hyperbranched polyglycerol-based multivalent cationic polymers and their interaction with DNA

Blood compatibility of novel water soluble hyperbranched polyglycerol-based multivalent cationic polymers and their interaction with DNA
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DOI:
10.1016/j.biomaterials.2006.06.021
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发表时间:
2006-11-01
期刊:
影响因子:
14
通讯作者:
Kizhakkedathu, Jayachandran N.
Kizhakkedathu, Jayachandran N.
中科院分区:
工程技术1区
文献类型:
--
作者:
Kainthan, Rajesh Kumar;Gnanamani, Muthiah;Kizhakkedathu, Jayachandran N.

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通过多分支阴离子开环聚合反应合成了一类基于聚甘油(PG)和聚乙二醇(PEG)的新型超支化聚合物。通过后胺化和季铵化反应在这些聚合物中添加了多价阳离子位点。使用不同浓度的这些聚合物进行的血液相容性研究表明,与支化阳离子聚乙烯亚胺(PEI)相比,它们对补体激活、血小板激活、凝血、红细胞聚集和溶血的影响不显著。季铵化程度对新型聚合物的血液相容性没有很大影响。这些聚合物的细胞毒性明显低于PEI,并且是聚合物中季铵化氮的函数。此外,这些聚合物在纳摩尔范围内与DNA结合,并且能够将DNA浓缩成60 - 80纳米范围内高度紧凑、稳定、水溶性的纳米颗粒。凝胶电泳研究表明,在所研究的条件下,无论季铵化百分比如何,它们在氮磷比约为1时与DNA形成电中性复合物。(c)2006爱思唯尔有限公司。保留所有权利。
A novel class of hyperbranched polymers based on polyglycerol (PG) and poly(ethylene glycol) (PEG) are synthesized by multibranching anionic ring opening polymerization. Multivalent cationic sites are added to these polymers by a post-amination and quarternization reactions. Blood compatibility studies using these polymers at different concentrations showed insignificant effects on complement activation, platelet activation, coagulation, erythrocyte aggregation and hemolysis compared to branched cationic polyethyleneimine (PEI). The degree of quarternization does not have large influence on the blood compatibility of the new polymers. Cytotoxicity of these polymers is significantly lower than that of PEI and is a function of quarternized nitrogen present in the polymer. Also, these polymers bind DNA in the nanomolar range and are able to condense DNA to highly compact, stable, water soluble nanoparticles in the range of 60-80 nm. Gel electrophoresis studies showed that they form electroneutral complexes with DNA around N/P ratio 1 irrespective of the percentage of quarternization under the conditions studied. (c) 2006 Elsevier Ltd. All rights reserved.