In Vitro Gene Delivery Mediated by Asialofetuin-Appended Cationic Liposomes Associated with γ -Cyclodextrin into Hepatocytes

Abstract

The purpose of this study is to evaluate in vitro gene delivery mediated by asialofetuin-appended cationic liposomes (AF-liposomes) associating cyclodextrins (CyD/AF-liposomes) as a hepatocyte-selective nonviral vector. Of various CyDs, AF-liposomes associated with plasmid DNA (pDNA) and γ -cyclodextrin ( γ -CyD) (pDNA/ γ -CyD/AF-liposomes) showed the highest gene transfer activity in HepG2 cells without any significant cytotoxicity. In addition, γ -CyD enhanced the encapsulation ratio of pDNA with AF-liposomes, and also increased gene transfer activity as the entrapment ratio of pDNA into AF-liposomes was increased. γ -CyD stabilized the liposomal membrane of AF-liposomes and inhibited the release of calcein from AF-liposomes. The stabilizing effect of γ -CyD may be, at least in part, involved in the enhancing gene transfer activity of pDNA/ γ -CyD/AF-liposomes. Therefore, these results suggest the potential use of γ -CyD for an enhancer of transfection efficiency of AF-liposomes.