Preparation Of Styearyl Alcohol Galactosidated Liposomes Loaded With Axitinib And Preliminary For Anti-hepatoma In Vitro

ObjectiveAxitinib is as the model drug in this experiment,and stearyl alcohol galacto is as the guide molecule to prepare Axitinib liposomes.The method improves the liposomes liver targeting efficiency and reduced side effects of chemical medicine.The freeze drying method increased stability of liposomes.The study obtained the better therapeutic effect.MethodsThe encapusulation efficiency was measured by sephadex filtration and high performance liquid chromatography.The preparation of liposomes was optimized by Box-Behnken response surface design experiment.The inhibitory effect of stearyl alcohol galactosidase modified Axitinib liposomes on growth of SMMC-7721 and A549 was tested by CCK-8 assay.Apoptosis of SMMC-7721 cells and A549 cells were assessed by Annexin V/PI flow cytometry.Expression of Bax,P53 and Bcl-2 in SMMC-7721 cells were detected by western blot.ResultsTo prepare stearyl alcohol galactosidase modified Axitinib liposomes by freeze drying,the average encapsulation efficiency is 69.34%,the average particle size is(145 ± 4.6)nm.The particle dispersion is stability and well-distributed.These results showed that stearyl alcohol galactosidase modified Axitinib liposomes prepared by the freeze drying could hold good physical and chemical properties.The liposomes preparation was optimized by Box-Behnken response surface design experiment.The best method was cholesterol : lecithin(mass ratio;1: 7.67),Axitinib to lecithin ratio(mass ratio;1: 21.50),the stearyl alcohol galactosidase to the lecithin(mass ratio;1: 16.69).The optimum temperature was 52.75 °C.According to the CCK-8 assay,it showed that the stearyl alcohol galactosidase modified Axitinib liposomes inhibited the growth of SMMC-7721 cells in time-dependent and concentration-dependent manner.The inhibition effect of stearyl alcohsidase modified axitinib liposomes on SMMC-7721 cells were higher than A549 under the same conditions,and also higher than the common liposomes and the drug substances.Annexin V/PI flow cytometry detected that the stearyl alcohol galactosidase modified Axitinib liposomes inhibited the growth of SMMC-7721 cells,and the inhibition result was better than the common liposomes as well as the drug substances.This further proved stearyl alcohsidase modified axitinib liposomes has liver targeting efficiency.Western blot showed that the expression level of Bax and P53 protein increased while Bcl-2 protein decreased with increasing concentration of the liposomes.ConclusionsStearyl alcohol galactosidase modified Axitinib liposomes had high encapsulation efficiency in the experiment.The stearyl alcohol galactosidase modified Axitinib liposomes inhibits the proliferation and induces the apoptosis of SMMC-7721 cells in vitro.The therapeutic effect was better than common liposomes and drug substances.The preliminary prove stearyl alcohol galactosidase modified Axitinib liposomes has liver targeting.