The stochastic effect of polydispersity on polymeric DNA delivery vectors

ABSTRACT The molecular composition and architecture of polymeric DNA delivery reagents govern their transfection efficiency. One parameter that is understudied is the influence of polydispersity on transfection efficiency. Here we report the synthesis of two molecularly identical polymer series, but with different polydispersities (1.3 vs. 2.0) and quantify the effect polydispersity on transfection efficiency. The results show that the effect of polydispersity on transfection efficiency in cell culture is not predictable and is stochastic in nature. In general terms, polymers with high polydispersity mediated higher levels of transfection in vitro compared to low polydispersity polymers with the same side chain distribution and composition. However, at higher molecular weights, the effect of polydispersity was polymer specific, with enhanced transfection efficiency in some cases, but negligible in others. An interesting outcome is that the higher polydispersity polymers generally enhanced the stability of polymer:DNA complexes and this enhancement generally correlated with enhanced transfection efficiency. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45965.