Department of Pharmaceutical Technology, Institute of Pharmacy, Friedrich-Schiller-University Jena, Otto-Schott-Str. 41, 07745 Jena, Germany; Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich-Schiller-University Jena, Humboldtstr. 10, 07743 Jena, Germany.
Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich-Schiller-University Jena, Humboldtstr. 10, 07743 Jena, Germany.
Carbohydr Polym. 2014 Nov 26;113:597-606. doi: 10.1016/j.carbpol.2014.07.048. Epub 2014 Jul 29.
Low molar mass linear poly(ethylene imine)s (lPEI) were grafted onto dextran via different synthesis routes aiming at the elucidation of structure-property relationships of dextran-graft-linear poly(ethylene imine) (dex-g-lPEI) conjugates for gene delivery applications. Beside the molar mass of well-defined lPEIs and the linker unit, also the amount of lPEI in the polymeric vectors was varied. The synthesized dextran modifications were characterized regarding their chemical structure and showed enhanced complexation and stabilization of DNA against enzymatic degradation. The transfection efficiency of dex-g-lPEIs was increased compared to unmodified lPEI and revealed a dependency of the used linking strategy. All complexes of DNA and dex-g-lPEIs were found to be nontoxic, but the synthesis route showed a strong influence on the aggregation of red blood cells. In conclusion, the linking strategy of lPEI to dextran has a significant impact on the physicochemical characteristics of DNA/polymer complexes, the biocompatibility as well as the transfection efficiency.
低摩尔质量线性聚（亚乙基亚胺）（lPEI）通过不同的合成途径接枝到葡聚糖上，旨在阐明用于基因传递应用的葡聚糖接枝线性聚（亚乙基亚胺）（dex-g-lPEI）缀合物的结构-性质关系。除了确定的 lPEI 的摩尔质量和连接单元外，聚合物载体中的 lPEI 含量也有所不同。合成的葡聚糖修饰物在化学结构方面进行了表征，并显示出对 DNA 的酶降解的增强的络合和稳定作用。与未修饰的 lPEI 相比，dex-g-lPEI 的转染效率得到了提高，并且揭示了所使用的连接策略的依赖性。所有 DNA 和 dex-g-lPEI 的复合物均被发现无毒性，但是合成途径对红细胞的聚集有很大影响。总之，lPEI 与葡聚糖的连接策略对 DNA/聚合物复合物的物理化学性质、生物相容性以及转染效率都有重大影响。
