Galactosylated polyethylenimine-graft-poly(vinyl pyrrolidone) as a hepatocyte-targeting gene carrier.

Polyethylenimine (PEI) has been used for the gene delivery system in vitro and in vivo since it has high transfection efficiency owing to proton buffer capacity. However, the use of PEI for gene delivery is limited due to cytotoxicity, non-specificity and unnecessary interaction with serum components. To overcome cytotoxicity and non-specificity, PEI was coupled with poly(vinyl pyrrolidone) (PVP) as the hydrophilic group to reduce cytotoxicity and lactose bearing galactose group for hepatocyte targeting. The galactosylated-PEI-graft-PVP (GPP) was complexed with DNA, and GPP/DNA complexes were characterized. GPP showed good DNA binding ability, high protection of DNA from nuclease attack. The sizes of DNA complexes show tendency to decrease with an increase of charge ratio and had a minimum value around 59 nm at the charge ratio of 40 for the GPP-1/DNA complex (PVP content: 4.1 mol%). The GPP showed low cytotoxicity. And GPP/DNA complexes were mediated by asialoglycoprotein receptors (ASGP-R)-mediated endocytosis. Also, the transfection efficiency of GPP-1/DNA complex at charge ratio of 40 in the HepG2 was higher than that of PEI/DNA one.