Size matters: Molecular weight affects the efficiency of poly(ethylenimine) as a gene delivery vehicle

Poly(ethylenimine) (PEI) samples of various molecular weights and pHs were used to transfect endothelial cells to achieve levels of gene expression fo r comparison. PEIs with nominal molecular weights of 600, 1200, 1800, 10,00 0, and 70,000 Da were examined at pHs of 5.0, 6.0, 7.0, and 8.0, and the re sults were recorded in terms of transfection efficiencies at 24, 48, 68, 92 , and 120 h post-transfection. Trials were performed on the human endotheli al cell-derived cell line EA.hy 926. We found that, for the polymers tested , transfection efficiency increased as the molecular weight of PEI increase d. Representative values of PEIs at pH 6 and molecular weight 70,000 produc ed average transfection efficiencies of 25.6 +/- 7.9% (n = 8) at the greate st average expression levels, while PEI of molecular weight 10,000 yielded efficiencies of only 11.4 +/- 1.7% (n = 6). Transfection efficiencies for m olecular weight 1,800 PEI were essentially zero, and PEIs of lower molecula r weights produced no transfection at all. In contrast, the pH of the PEI s olutions had no discernible effect on transfection. Optimal expression of t he green fluorescent protein reporter occurred between 2 and 3 days post-tr ansfection. The amount of reporter expression also was noted, as determined by the brightness of fluorescing cells under UV. The data obtained demonst rate that the molecular weight of the PEI carrier has an effect on transfec tion efficiency while the pH of the PEI solutions prior to DNA complexation has no such effect. (C) 1999 John Wiley & Sons, Inc.