Protection of oligonucleotides against enzymatic degradation by pegylated and nonpegylated branched polyethyleneimine

Among the cationic polymers, polyethyleneimine (PEI) is a promising candidate for delivery of oligodeoxynucleotides (ODNs). In this study, we wondered whether pegylation of PEI influences the complexation with ODNs. We especially aimed to investigate whether ODNs are differently protected against enzymatic degradation in PEI and polyethylene glycol-polyethyleneimine (PEG-PEI) polyplexes. Using fluorescence resonance energy transfer combined with fluorescence correlation spectroscopy, we found that PEI/ODN polyplexes remain to protect the ODNs they carry over a prolonged period of time while in PEG-PEI/ODN polyplexes the degradation of the ODNs slowly proceeds. We attribute this to the fact that PEI seems to compact the ODNs more firmly in the polyplexes' core than PEG-PEI, which apparently also results in a better protection against enzymatic degradation. These observations may also influence the efficiency of PEI-based ODN delivery in vivo, where pegylation is an attractive strategy to enhance the stability of the polyplexes in the blood stream.