Galactosylated chitosan-g-PEI/DNA complexes-loaded poly(organophosphazene) hydrogel as a hepatocyte targeting gene delivery system in vitro and in vivo

摘要

Hydrogels have been widely used in drug delivery systems because they can control the release and thereby enhance the efficiency of locally delivered bioactive molecules such as therapeutic drugs, proteins, or genes by loading of them in the hydrogels. For gene delivery, localized release of plasmid DNA or polymer/DNA complexes can transfect cells with sustained production of tissue inductive proteins. This report investigates the galactosylated chitosan-graft-polyethylenimine (GC-g-PEI)/DNA complexes-loaded poly(organophosphazene) thermosensitive biodegradable hydrogel as a hepatocyte targeting gene delivery system. GC-g-PEI/DNA complexes-loaded hydrogel showed low cytotoxicity. Also, higher transfection efficiency of GC-g-PEI/DNA complexes-loaded hydrogel was obtained compared to PEI/DNA complexes-loaded one. Furthermore the GC-g-PEI/DNA complexes-loaded hydrogel system showed good hepatocyte specificity in vitro and in vivo. Our results indicate that the GC-g-PEI/DNA complexes-loaded hydrogel system has the potential to be a safe and efficient hepatocyte targeting gene delivery system.