AIM:To develop a novel non-viral gene delivery system,which has a small particle size and a high transfectionefficiency to hepatocyte and hepatoma cells.METHODS:Lipid-polycation-DNA lipopolyplex (LPD) wasprepared by mixing plasmid DNA and polylysine.The resultedpolyplex was incubated for 10 min at room temperature,following the addition of preformed cationic liposomes.Themorphology of LPD was observed by transmission electronmicroscopy.The diameter and surface charge of LPD weremeasured by photon correlation spectroscopy (PCS).Thenuclease protection ability of LPD was evaluated by agarosegel electrophoresis.Estimation of the transfection efficiencywas performed by galactosidase assay in Chang cells andSMMC-7721 cells.RESULTS:LPD had a regular spherical surface.The averagediameter and the zeta potential of LPD were 132.1nm and26.8mV respectively.LPD could protect plasmid DNA fromnuclease degradation after 2 hours incubation at 37℃ whilethe naked DNA degraded rapidly.The average transfectionefficiencies were 86.2±8.9% and 72.4±6.5% in Chang cellsand SMMC-7721 cells respectively.CONCLUSION:LPD has a rather small particle size and ahigh transfection activity.LPD may be a good non-viral vectorfor application in some gene delivery. AIM: To develop a novel non-viral gene delivery system, which has a small particle size and a high transfection efficiency to hepatocyte and hepatoma cells. METHODS: Lipid-polycation-DNA lipopolyplex (LPD) wasprepared by mixing plasmid DNA and polylysine. The resulting polyplex was incubated for 10 min at room temperature, following the addition of preformed cationic liposomes. Theology of LPD was observed by transmission electronmicroscopy. The diameter and surface charge of LPD weremeasured by photon correlation spectroscopy (PCS) .Thenuclease protection ability of LPD was evaluated by Agarosegel electrophoresis. Estimation of the transfection efficiency was performed by galactosidase assay in Chang cells and SMMC-7721 cells. Results: LPD had a regular spherical surface. The average dose and the zeta potential of LPD were 132.1 nm and 26.8 mV respectively. LPD could protect plasmid DNA fromnuclease degradation after 2 hours incubation at 37 ° C while the naked DNA degraded rapidly. the average transf LPD has a rather small particle size and ahigh transfection activity. LPD may be a good non-viral vector for application in some gene delivery.