The effect of cationic charge density change on transfection efficiency of polyethylenimine

Polyethylenimine (PEI) is a potent non-viral gene delivery carrier. PEI surface charge plays a major role in its condensation ability which in turn is a necessary requirement for high transfection efficiency. As the PEI charge density is dependent on pH, the effect of pH changing PEI on PEI condensation ability, transfection efficiency, and cytotoxicity was investigated.

In order to compare the different values of pH, 25 kDa PEI solutions were prepared at the pH values of 5, 7 and 10, afterward complexed with two plasmids encoding reporter genes of luciferase and enhanced green fluorescence protein to evaluate the capability of polymers in plasmid delivery at two incubation time (4 versus 24 hr).

The condensation ability of PEI in acidic, neutral and basic environments was similar. At low pH value, the polyplex had negative surface charge whereas at a higher pH value, the surface charge increased and became positive. The higher transfection efficiency and lower cytotoxicity were achieved by the polyplexes prepared at the pH value of 5 with longer incubation time of 24 hr.

The results showed the impact of pH value of PEI on biological and biophysical properties of polyplexes. Although the proton sponge effect can justify several properties of PEI, these results suggest that the proton sponge hypothesis may not be applicable for polymers with low buffering capacity at the pH values around 5.