PEG5000-grafted-Chitosan/DNA complexes for liver targeted gene delivery

Abstract

In recent years, the potential of chitosan as a carrier for gene delivery to liver has been extensively studied in vitro. However, the gene transfection efficiency of chitosan in liver is still limited by the low stability of chitosan/DNA complexes in vivo. Therefore, PEG (Polyethylene glycol) 5000 was grafted onto chitosan to increase the stability of chitosan/DNA complexes in blood and bile. In addition, surface crosslinking was applied to the PEG-g-chitosan/ DNA complexes to increase the lateral stability. In HepG2 cell lines, the transfection efficiency of PEG5000-grafted-chitosan/ DNA complexes was at the same level as that of unmodified chitosan. In animal studies, both PEG5000-grafted-chitosan/ DNA complexes and chitosan/ DNA complexes were administrated through bile duct and portal vein to rat livers. The PEG5000-grafted-chitosan/ DNA complexes injected via bile duct showed improved gene expression in rat liver compared with unmodified chitosan. For portal vein injection, gene expression was only observed in rats injected with PEG5000-grafted-chitosan/ DNA complexes.