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

被引:233
作者
Kainthan, Rajesh Kumar
Gnanamani, Muthiah
Ganguli, Munia
Ghosh, Tanay
Brooks, Donald E.
Maiti, Souvik
Kizhakkedathu, Jayachandran N.
机构
[1] CSIR, Inst Genom & Integrat Biol, New Delhi 110007, India
[2] Univ British Columbia, Ctr Blood Res, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada
[3] Univ British Columbia, Dept Pathol & Lab Med, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada
[4] Univ British Columbia, Dept Chem, Life Sci Ctr, Vancouver, BC V6T 1Z3, Canada
基金
加拿大健康研究院; 加拿大创新基金会;
关键词
hyperbranched polymers; cationic polymers; blood-compatibility; drug delivery; DNA; AFM;
D O I
10.1016/j.biomaterials.2006.06.021
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
收藏
页码:5377 / 5390
页数:14
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