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聚乙烯亚胺提高质粒DNA生物利用度效率的比较分析

Comparative Analysis of Polyethyleneimine Efficiency for Improvement of Plasmid DNA Bioavailability.

作者信息

Ustinova T M, Yuidin M A, Vengerovich N G, Stepanov A V, Gadzikovskii S V

机构信息

State Research Testing Institute of Military Medicine, Ministry of Defense of the Russian Federation, St. Petersburg, Russia.

Silver Pharm Company, St. Petersburg, Russia.

出版信息

Bull Exp Biol Med. 2018 Mar;164(4):473-477. doi: 10.1007/s10517-018-4015-z. Epub 2018 Mar 6.

Abstract

We studied the influence of the type and structure of polyethyleneimine on bioavailability and expression of plasmid DNA carrying IGF-1 gene. Polymers with different molecular weights (2.5, 10, 25, and 60 kDa) of linear and branching structure were studied. It was found that the time of polyplex circulation in the blood did not exceed 24 h and the maximum concentration of plasmid DNA was attained with complexes with a molecular weight of 60 kDa. Analysis of liver samples showed that administration of 60-kDa branched polyethyleneimine complex provides DNA protection from degradation for 4 h; in 24 h from the start of the experiment, its concentration was significantly higher than the concentration of other studied polyethyleneimines. The expression of plasmid IGF-1 DNA for this complex attained maximum in 4 h and was equal to 15.50 (7.98; 21.98) arb. units/ml. These results allow us to recommend using polyethyleneimines with branched structure and a molecular weight of 60 kDa for improving plasmid DNA protection and bioavailability.

摘要

我们研究了聚乙烯亚胺的类型和结构对携带IGF-1基因的质粒DNA生物利用度和表达的影响。研究了具有不同分子量(2.5、10、25和60 kDa)的线性和分支结构的聚合物。结果发现,多聚体在血液中的循环时间不超过24小时,分子量为60 kDa的复合物可使质粒DNA达到最大浓度。肝脏样本分析表明,给予60 kDa分支聚乙烯亚胺复合物可使DNA在4小时内免受降解;在实验开始后的24小时,其浓度显著高于其他研究的聚乙烯亚胺的浓度。该复合物的质粒IGF-1 DNA表达在4小时达到最大值,为15.50(7.98;21.98)相对单位/毫升。这些结果使我们推荐使用具有分支结构和60 kDa分子量的聚乙烯亚胺来提高质粒DNA的保护作用和生物利用度。

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