Enhancement of polyethylene glycol (PEG)-modified cationic liposome-mediated gene deliveries: effects on serum stability and transfection efficiency

Abstract

In this study, we modified cationic liposomes either by polyethylene glycol (PEG)‐grafting or PEG‐adding methods, and compared the physical properties of transfection complexes and transfection efficiency in‐vitro and prolonged circulation in‐vivo. The PEG‐grafted transfection complexes were prepared by mixing plasmid DNA with PEG‐grafted cationic liposomes, which were composed of DSPE‐PEG 2000 and cationic lipids. The PEG‐added transfection complexes were prepared by adding DSPE‐PEG 2000 to the mixture of cationic liposomes and plasmid DNA. The particle sizes of the PEG‐modified transfection complexes (˜200 nm) changed a little over 4 weeks compared with the conventional transfection complexes. In the presence of serum, the transfection efficiency of the conventional transfection complexes was lowered whereas the transfection efficiency of the PEG‐modified transfection complexes was maintained. Moreover, the transfection efficiency of the conventional transfection complexes was significantly reduced when they were stored. However, the transfection efficiency was stable for the PEG‐modified transfection complexes, even after two weeks of storage. Of the in‐vitro transfection efficiencies, there was no difference between PEG‐grafted and PEG‐added transfection complexes. When the conventional, PEG‐grafted, and PEG‐added transfection complexes were administered into mice by the tail vein, the PEG‐added transfection complexes showed a prolonged circulation of plasmid DNA compared with other transfection complexes. These results suggest that the PEG‐added transfection complexes could be a useful non‐viral vector because of their simplicity in preparation, enhanced stability and prolonged circulation compared with the conventional transfection complexes.