PEGylation of Poly(ethylene imine) Affects Stability of Complexes with Plasmid DNA under in Vivo Conditions in a Dose-Dependent Manner after Intravenous Injection into Mice

The influence of PEGylation on polyplex stability from poly(ethylene imine), PEI, and plasmid DNA was investigated both in vitro and after intravenous administration in mice. Polyplexes were characterized with respect to particle size (dynamic light scattering), zeta-potential (laser Doppler anemometry), and morphology (atomic force microscopy). Pharmacokinetics and organ accumulation of both polymers and pDNA were investigated using 125I and 32P radioactive labels, respectively. Furthermore gene expression patterns after 48 h were measured in mice. To elucidate the effect of different doses, all experiments were performed using ca. 1.5 μg and 25 μg of pDNA per mouse. Our studies demonstrated that both PEI and PEG−PEI form stable polyplexes with DNA with similar sizes of 100−130 nm. The zeta potential of PEI/pDNA polyplexes was highly positive, whereas PEG−PEI/pDNA showed a neutral surface charge as expected. The pharmacokinetic and organ distribution profiles after 2 h show similarities for both PEI and ...