Preparation Of Oxaliplatin Liver-targeting Liposomes And Its Pharmacodynamic Preliminary Study In Virtro

ObjectiveIn this study, used the laboratory-made styearyl alcohol galactosidase asthe liver-targeting guide molecule to prepare oxaliplatin liver-targeting liposomeswhich were modified with the stearyl alcohol galactosidase, to improve theliver-targeting of oxaliplatin, to reduce the toxicity and side effect and to obtainthe best therapeutic effect.MethodsConducted prior to the prescription of oxaliplatin study and conductedverification methodology, the method of determination of oxaliplatin wasestablished and studied its physical and chemical properties. Dextran gelmicrocolumn centrifugation-HPLC was employed to detect the entrapmentefficiency of oxaliplatin liver-targeting liposomes. The encapsulation efficiencywas used as the index to choose a suitable method for preparing liposomes, onthe basis of single factor investigation, Box-Benhnken experimental designmethod was applied to optimize the preparing prescription of oxaliplatinliver-targeting liposomes. In accordance with the selected optimal prescriptionpreparation of liposomes, investigated the morphology, the particle size, theencapsulation efficiency and other physical and chemical properties ofoxaliplatin liver-targeting liposomes. Used the cultured human hepatocellular carcinoma cell line SMMC-7721in vitro as the research object, by MTTcytotoxicity assay and flow cytometry apoptosis, explored the inhibited rate andextent of apoptosis of oxaliplatin liver-targeting liposomes which were modifiedwith stearyl alcohol galactosidase on human hepatoma SMMC-7721at thecellular level. Investigated the targeting property of liposomes initially.ResultsThis experiment has established the best method for the determination ofcontent of oxaliplatin into. Dextran gel microcolumn centrifugation-HPLC wassuitable for the determination of oxaliplatin liver-targeting liposomesencapsulation efficiency. The optimal prescription condition of oxaliplatinliver-targeting liposomes which was obtained by the Box-Benhnkenexperimental design method as follows: phospholipids mass concentration was10.34g·L-1, the mass ratio of lipids to oxaliplatin was30.9:1and the ratio oflipids to18-Gal was21.5:1. The average encapsulation efficiency of oxaliplatinliver-targeting liposomes was76.7%, the average particle size was198.4nmand morphological observation by electron microscopy was spherical or nearlyspherical. The results of MTT cytotoxicity test showed that the inhibition rate ofoxaliplatin liver-targeting liposomes on SMMC-7721cell was significantly betterthan the inhibition rate of conventional liposomes or free oxaliplatin. The resultof Flow cytometry experiments showed that under the effect of the sameconcentration, oxaliplatin liver-targeting liposomes could induce more cellapoptosis. Initially identified that oxaliplatin liver-targeting liposomes werecapable of liver targeting.ConclusionsIn this experiment, the oxaliplatin liver-targeting liposomes which weremodified with the stearyl alcohol galactosidase had high encapsulationefficiency, its particle size distribution was uniformed, the liposomes could obviously inhibit the growth of hepatocellular carcinoma cells and induceapoptosis of hepatocellular carcinoma cells, the oxaliplatin liver-targetingliposomes had certain liver targeting property.