The Preparation And Evaluation Of Ginsenosides Rg₃-loaded Long-circulating Liposomes

ObjectiveGinsenoside Rg3(G-Rg3)was the active ingredient extracted from the stems and leaves of Ginseng.Clinical experiments results showed that G-Rg3 has strong anti-cancer activity.It can inhibit the proliferation,invasion,metastasis of the liver cancer,lung cancer and gastric cancer etc.,and can improve cardiovascular functions and enhance the immunity.In order to prolong the drug circulation time so as to improve its bioavailability,G-Rg3-loaded long-circulating liposomes were prepared in this study.MethodG-Rg3-loaded long-circulating liposomes were prepared by film dispersion method.Firstly,the film-forming temperature,hydration temperature and pH of PBS were selected by the single factor investigation.Then a Box-Behnken Design with three factors and three levels were used to optimize the prescription of G-Rg3-loaded long-circulating liposomes.The phospholipids and cholesterol ratio(A),the concentration of DSPE-PEG2000(B),and the phospholipids and G-Rg3 ratio(C)were defined as independent values.The entrapment efficiency(EE)and drug-loading amounts(OD)were defined as the evaluation indexes.The particle size,Zeta potential and in vitro release experiments were also determined in this study.To improve the stability of the liposomes,G-Rg3 long circulating lipids were dried by the freeze-drying technique and the lyoprotectants were screened.The preliminary pharmacokinetic study of the liposomes was investigated in SD rats after administration via caudal vein injection.ResultThe optimal formulation of G-Rg3-loaded long-circulating liposomes was phospholipids:cholesterol=14:1,phospholipids:G-Rg3=8:1,and the concentration of DSPE-PEG2000 was 5%.The liposomes showed spherical shape with narrow particle size distribution.The particle size,Zeta potential,encapsulation efficiency and drug-loading rate were 44.57±1.37 nm,-26.45±1.49 mv,85.24±1.02%and 7.44 ±0.08%,respectively.The effects of different lyoprotectant were studied,and 2%lactose was selected.The results of in vitro dissolution curve showed,compared with the G-Rg3-loaded liposomes,G-Rg3-loaded long-circulating liposomes have sustained-release effect.Pharmacokinetic statistical analysis showed that Cmax,AUC,t1/2 and MRT of G-Rg3 long-circulating liposomes group were 19.70 ?g·mL-1,17.04?g·h·mL-1,1.68 h and 2.32 h,respectively,which was higher than G-Rg3 liposomes drug group(13.96 ?g·mL-1,10.40 ?g·h·mL-1,1.53 h,2.09 h)? G-Rg3 group(5.21?g·mL-1,4.81 ?g·h·mL-1,1.12 h,1.43 h).The CL of three croups were 532.27 h-1·Kg-1,839.36 h-1·Kg-1 and 1190.09 h-1·Kg-1,respectively.ConclusionThe process of G-Rg3 long-circulating liposomes which prepared by film dispersion method was simple and feasible.The liposomes showed small size,uniform distribution,high encapsulation efficiency and long circulation time.The pharmacokinetic study data indicated the G-Rg3 long-circulating liposomes significantly enhanced the bioavailability of G-Rg3.