A Novel Cationic Liposome For Gene Delivery

Cationic liposome-DNA(CL-DNA)complexes are being used for nonviral gene delivery systems focused on applications that include clinic trials and experimental medium.Being different from most liposomes,viral vectors have achieved high cell transfection efficiency in vitro.To overcome several drawbacks encountered by viral vectors in safe gene therapy of clinical trials,non-viral gene delivery vectors are considered to be alternative and offer many potential advantages for transfering functional DNA into cells in living animals.Although many cationic liposomes have been exploited for gene transfer,their efficeincies and pharmacokinetics are expected to be improved.In order to increase the drug loadings and reduce side effects,We selected polymers glyceride as substrates to synthesis cationic liposomes.Decapolyglycerol monostearate is a kind of food additives,which is widely used in making ice cream,candy,soft drinks and dairy products.In this study,a series of cationic decapolyglycerol monostearates with a gradient of nitrogen content were synthesized via N,N’-carbonyldiimidazole catalytic reaction and they are named CDGMS.We investigated physico-chemical properties of the DNA complexes formulated by this particular type of amino modified lipids aiming to understand their structure-fonction relationships.This novel liposome is detected with small particle size and proper surface potential compared with Lipofectamine 2000.In the experiments comparing the release of DNA from DNA/liposome complexes,a smaller fraction of DNA was released from DNA/CDGMS complexes than that from DNA/Lipofectamine 2000 either in physiological or electrolytic dissociation condion.Moreover,These liposomes encapsulated large masses of DNA,which was 1.67～2.42 folds more than that was encapsulated by Lipofectamine 2000.The obtained data show that cytotoxicity of CDGMS is lower than Lipofectamine 2000 and this liposome can be applied in vivo without causing death.In plasmid DNA(pDNA)transfection experiment,CDGMS transfection efficiency is equivalent to to Lipofectamine 2000.In order to explain why the CDGMS can transfect plasmid DNA into cells with high efficiency,We identify that CDGMS enabled DNA to escape from endosome efficiently.