Department of Pharmaceutical Technology and Biopharmacy, Friedrich Schiller University Jena, Lessingstrasse 8, 07743 Jena, Germany.
Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Philosophenweg 7, 07743 Jena, Germany; Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743 Jena, Germany.
Eur J Pharm Biopharm. 2018 Dec;133:112-121. doi: 10.1016/j.ejpb.2018.10.003. Epub 2018 Oct 9.
To gain a more profound insight into the impact of the number and the density of protonable amines on the performance of polycations as non-viral vectors, a series of linear poly(ethylene imine)s (LPEIs) with different numbers of ethylene imine (EI) units was compared to partially hydrolyzed (21 to 86%, 20 kDa) poly(2-ethyl-2-oxazoline)s (PHPEtOxs) with a corresponding number of EI units but with varying densities. PHPEtOx polyplexes demonstrated lower transfection efficiencies than the corresponding LPEIs although having the same number of EI units as LPEI, exhibiting smaller or comparable polyplex diameters, similar zeta potentials, and similar or even preferred cyto- and hemocompatibility profiles. The lower efficiency was found to be related to a lower DNA binding capacity and less efficient protection of plasmid DNA against enzymatic degradation. The direct comparison of both types of polymers revealed that the density of charges within the polymer backbone seems to be more important than the total number of EI units. In conclusion, the reduction of the EI density to produce more biocompatible polyplexes must be critically examined, since the presence of high numbers of EI next to each other seems to have a dramatically higher impact on the transfection efficiency than on the in vitro toxicity.
为了更深入地了解质子化伯胺的数量和密度对聚阳离子作为非病毒载体性能的影响，将一系列具有不同乙撑亚胺（EI）单元数的线性聚（乙撑亚胺）（LPEI）与具有相应数量的 EI 单元但具有不同密度的部分水解（21 至 86%，20 kDa）聚（2-乙基-2-恶唑啉）（PHPEtOxs）进行了比较。尽管 PHPEtOx 聚阳离子与 LPEI 具有相同数量的 EI 单元，但转染效率却低于相应的 LPEI，表现出较小或相当的聚集体直径、相似的 ζ 电位以及相似甚至更优的细胞和血液相容性特征。发现较低的效率与较低的 DNA 结合能力和对质粒 DNA 免受酶降解的保护效率较低有关。两种类型聚合物的直接比较表明，聚合物主链内的电荷密度似乎比 EI 单元的总数更为重要。总之，必须仔细检查降低 EI 密度以产生更具生物相容性的聚集体的做法，因为大量 EI 彼此相邻似乎对转染效率的影响远大于对体外毒性的影响。
