Effect of polyethylene glycol on gene delivery of polyethylenimine

Polyethylene glycol (PEG) has been coupled to many cationic polymers such as polyethylenimine (PEI) to improve the stability and transfection efficiency. We prepared PEG-grafted PEI with different lengths and amounts of PEG and used these graft copolymers as nonviral gene vectors. We measured the complex size and zeta-potential of polymer-DNA complexes in the presence of salt to estimate the stability of polymer-DNA complexes. We also investigated the cytotoxicity and transfection efficiency in C3 cells. In the case of graft copolymers, the stability of polymer-DNA complexes and transfection efficiency were affected by the graft length and amount of PEG side chain. PEG side chains stabilize the polymer-DNA complexes in the presence of salt, but the longer PEG side chains also interrupt the gene delivery in the cells due to the more efficient steric hindrance by longer PEG side chains, and therefore the transfection efficiency is decreased. Short PEG side chains with molecular weight of 350 kDa stabilized the polymer-DNA complexes without decreased transfection efficiency.