Optimized dextran-polyethylenimine conjugates are efficient non-viral vectors with reduced cytotoxicity when used in serum containing environments
- 作者：Dahai Jiang ; Aliasger K. Salem ; aliasger-salem@uiowa.edu
- 关键词：Dextran ; Polyethylenimine ; PEI ; Gene delivery ; Cationic polymer ; Transfection ; Plasmid DNA ; pDNA ; Serum ; Complexes ; Nanoparticles ; Nanoplexes ; Gene delivery ; Non-viral
- 刊名：International Journal of Pharmaceutics
- 出版年：2012
- 期刊代码：24_03785173
- 类别：pha
- 出版时间：1 May, 2012
- 卷：427
- 期：1
- 页码：71-79
- 文件大小：886 K
摘要
Polyethylenimine (PEI) is a cationic polymer that is an efficient transfection reagent marred by high toxicity and a susceptibility to aggregate in the presence of serum. Dextran is a biodegradable natural polysaccharide that can be used to reduce the toxicity of PEI and increase its stability in the presence of serum. In this study, small branched PEI units (800/2000 Da) were attached to dextran (Dex; 15/100-200 kDa) to form dextran-polyethylenimine (Dex-PEI) conjugates. The Dex-PEI conjugates were then tested as a gene carrier in the model HEK293 cell line. Dex-PEI conjugates displayed significantly lower cytotoxicity than PEI (25k). Both Dex-PEI and PEI efficiently delivered firefly luciferase encoded plasmid DNA (pDNA) to the HEK293 cells. Dex-PEI resulted in moderately lower transfection efficiencies than PEI 25k when the transfection was carried out in media without serum for 4 h. However, in the presence of serum, which more accurately predicts the anticipated environment of non-viral vectors in vivo, Dex-PEI and unmodified PEI generated similar transfection efficiencies when incubated with the cells for 4 h. When the incubation time of the vectors was increased to 48 h, significantly higher transfection efficiencies were generated by Dex-PEI in comparison to PEI. Turbidity measurements showed that complexes formed between plasmid DNA and unmodified PEI were more susceptible to aggregation in serum-containing media than complexes formed from pDNA and Dex-PEI. Dex-PEI conjugates are therefore believed to have greater potential for translational applications because of lower cytotoxicity characteristics and improved stability in serum containing environments.