The Study Of Targeting Long-acting Matrine Iposome And Pharmacodynamics

ObjectiveMatrine injection used to treat liver fibrosis in vivo have some defects, such as widely distributed, easily metabolism, side effects and so on. For this reason, a long-acting matrine liposome was prepared in this work, which can orient the hepatic stellate cells and increase the concentration of matrine in the hepatic stellate cells. According to the effect of martine liposome on the proliferation of hepatic stellate cells in vitro, the anti-liver fibrosis effect of martine liposome can evaluated. And this work could provide experimental evidences of the pharmacodynamics for the development of novel preparations of matrine anti-liver fibrosis.MethodsMatrine liposome was prepared and the film of the liposomes was observed. The differences of these preparations, film dispersion method, reverse evaporation method, ethanol injection method, and ethyl ether injection method were investigated. Taking encapsulation efficiency as the marker the best prescription and process was optimized with orthogonal experimental design method. And the long-acting matrine liposome was prepared with reverse evaporation method. The resolution between drug-containing liposome and free drug was explored by the chromatography, microcolumn centrifugation, the high-speed centrifugation and dialysis method; the effect of the eluent on encapsulation rate of matrine liposome was studied with HPLC through microcolumn centrifugation and segmented collection of centrifugal; the appearance of liposome was observed by TEM with negative staining; the particle diameter of liposome was measured by dynamic light scattering method; the in vitro release of the liposome was examined by dynamic dialysis method; stability of Liposome was compared under the conditions of room temperature and3℃. Under the condition:10%DMEM culture liquid was cultured at37℃,5%CO2incubator, the inhibitory effect of the new matrine liposome on hepatic stellate cells was studied by inhibition rate.ResultsThe matrine liposome was prepared with reverse evaporation technique. One optimum recipes of long-acting matrine liposome, obtained from orthogonal experimental design, showed that cholesterol/lecithin8:1, cholesterol/matrine8:1, pH6.8under the optimum conditions is0.055±0.005Mpa,40℃,100r/min for1h. The results showed that using the defined method, we prepared the matrine liposome with new dosage form:it has round, oval-shaped particles with average particle size of about100nm through TEM. Research indicated that the measuration of encapsulation efficiency is reliable, and measured the encapsulation efficiency is80%or more. Using HPLC we found that both the peak figure of drug and standard curve were ideal, the liposome was separated well with0.9%NaCl solution as a micro-column centrifugal elution solvent. In vivo experiment showed that long-acting matrin liposome targeting and long-acting matrine liposome can inhibit the grown of hepatic stellate cells.ConclusionNew dosage form technology for matrine of reverse-phase evaporation method is feasible, the experiment results of hepatic stellate cells show that the effects of new dosage form for matrine was better than that of conventional matrine and the purpose of the trial design had achieved.