| Ginsenoside Rh2(G-Rh2)was the trace active ingredient that was extracted from the stems and leaves of ginseng.With strong anti-cancer activity,G-Rh2 can inhibit tumor proliferation,induce differentiation and apoptosis,reverse drug resistance and etc..G-Rh2 has the proliferation inhibition effect on many cancer cells such as lung cancer,liver cancer,breast cancer,leukemia,colon cancer,nasopharyngeal cancer,prostate cancer and etc.It had become one of the hotspots in anti-cancer drug research field.This paper reviewed the anti-tumor mechanism and formulation research of G-Rh2.G-Rh2 is lipid-soluble drugs with poor solubility,which limited its clinical applications.In order to prolong the time of in vivo drug action and improve its bioavailability.G-Rh2 liposomes were prepared.The optimal conditionsion and the quality of the liposomes were screened and evaluated,respectively.The preliminary pharmacokinetics were also investigated in this paper.G-Rh2 liposomes with light blue opalescent were successfully prepared by film dispersion method.HPLC was utilized to determine the content of G-Rh2 with mobile phase of acetonitrile:water:phosphoric acid = 550:450:1.25,flow rate of 1 mL·min-1 and detection wavelength at 203 nm.The encapsulation efficiency of G-Rh2 liposomes was measured by micro column centrifugation method.G-Rh2 liposomes and G-Rh2 can be separated well by this method,and the average recovery rate of micro column was 98.29%.The ultrasonic time and hydration temperature was confirmed to be 40 ?,15 min respectively by the single factor investigation with the encapsulation efficiency and particle size as the evaluation indexes.The optimization study was performed using a Box-Behnken design in order to find the optimal conditions.The encapsulation efficiency and particle size were defined as response values.The phospholipids and cholesterol ratio(A),the phospholipids and G-Rh2 ratio(B),and pH of PBS(C)defined as independent values were evaluated on two response.The experiment was designed and analyzed by Design-Expert 8.0.6.The software predicted the optimum A,B,C was 30:1,10:1,8.0,respectively.The encapsulation efficiency and particle size of desirability value was 88.75%,161.4 nm,respectively.The optimal conditions was validated by validation experiments:the encapsulation efficiency and particle size was 85.53 ± 1.14%and 175.73 ± 2.95 nm,respectively.The result was little difference between desirability value.The transmission electron microscopy(TEM)of G-Rh2 liposomes showed that liposomes were spherical or Similar spherical shape with the particle size around 200nm.In vitro release experiments of G-Rh2 and G-Rh2 liposomes were studied in PBS(pH 7.4).The results showed that compared with the G-Rh2 drug,G-Rh2 liposomes have sustained-release effect.The cumulative release rate G-Rh2 liposomes was 84.31 ± 2.41%at 72 h.The Zeta potential of G-Rh2 liposomes was also determined and the result is-40.67±1.53mV.To improve its stability,freeze-dried powder of G-Rh2 liposomes were prepared.The effects of different lyoprotectant was studied,and 4%sucrose was selected.lyophilized powder of G-Rh2 liposomes showed smooth appearance,better dispersing effect and particle size.The encapsulation efficiency had small change before and after freeze-drying.The Preliminary pharmacokinetic study of G-Rh2 liposomes was investigated in wistar rats.After administration via caudal vein injection,the blood concentration was determined by HPLC.And pharmacokinetic parameters was analysised by Winnonlin 5.2 Pharmacokinetic statistical analysis software.Compared with that of G-Rh2 drug group,Tmax,Cmax,T1/2,AUClast and AUMClast of G-Rh2 liposomes group were all significantly improved.The time of in vivo drug action was prolonged significantly.These data indicated the bioavailability of G-Rh2 was improved.These studies may contribute to the development of G-Rh2 preparations. |
PDF Full Text Request