| ObJective : By emulsifying-solvent evaporating method,the solid particle stabilized emulsion(Pickering emulsion)was taken as a template,PLGA(Poly Lactic acid-Poly Glycolic acid)was taken as a structural material to make porous microspheres containing mangiferin,so as to achieve the sustained release of mangiferin,to reduce the effect of it on intestinal flora metabolism.Method:1.the influencing factors of Pickering emulsion template and blank PLGA porous microspheres were studied,which is prepared by two-step method,to determine the preparation process and prepare the blank PLGA porous microspheres.at the same time,to Investigate the easier process,which is by one-step method,and to try to use the one-step method to prepare the blank PLGA porous microspheres.2.The preparation processes of porous microspheres containing mangiferin was evaluated,packing suspension method,packing saturated solution method and saturated solution adsorption method were attempted to prepare drug loaded microspheres,the method of determining the content of mangiferin in the drug loaded microspheres was established,and the drug loading rate and entrapment rate of the microspheres prepared by three different processes were determined.3.The drug loaded microspheres prepared by the final process wereinvestigated by in vitro release test,comparing with the drug substance,whether there is a sustained release effect.4.By intestinal metabolism test,the effect of intestinal metabolism of mangiferin in the drug loaded microspheres was studied,whether the effect could be reduced by the drug loaded microspheres.Results:1.Double Pickering emulsion was taken as a template to prepare blank PLGA porous microspheres successfully via two-step method,and preparation process was optimized.The best proportion of the material was obtained: H30 Hydrophobic silica(g)/Intermediate oil phase(ml)=1/200;Internal water(ml)/Intermediate oil phase(ml)=1/2;N20 Hydrophilic silica(g)/External water phase(ml)=1/200;initial emulsion(ml)/External water phase(ml)=1/4;PLGA(g)/dichloromethane(ml)=1/20?However,one-step method could not prepare porous microspheres,but solid microspheres.2.In the three different porous microspheres containing mangiferin prepared by packing suspension method,packing saturated solution method and saturated solution adsorption method,the drug loading rate were 0.21%?0.08%?0.05%,and the entrapment rate were 16.15%?41.12%?25.70%.Considering from the point of maximum drug loading rate,packing suspension method was determined as the final process.3.Through the in vitro release test,comparing with the drug substance,it was found that the drug loaded microspheres had no significant sustained release effect on 15 min.The maximum cumulative release rates of the drug loaded microspheres and the drug substance were reached after 15 min,and there was no significant change in the maximum cumulative release rates from 15 min to 24 h.But in 24 h,the maximum cumulative release rate of drug substance was nearly 100%,the drug loaded microspheres' was about 84%,the drug substance in the drug loaded microspheres are not fully released.In the T test(n=3),t=48.24,P=0.0000,variance of the maximum cumulativerelease rate of the drug group and the microsphere group were statistically significant at the a=0.05 level,and the difference between the two groups was statistically significant.4.Through the intestinal metabolism test,comparing with the drug substance group,it was found that the concentration of mangiferin of the microspheres group decreased more slowly slightly in the intestinal flora fluid.when the metabolic time was 4h,the mangiferin in the drug substance group was completely metabolized,while the concentration of 0.00077mg/ml remained in the microspheres group.The T concentration(n=3),t=97.03,P=0.0000,and variance of the residual concentration of mangiferin in the drug substance group and the microsphere group at the reaction time of 4h were analyzed,and the difference was statistically significant at the a=0.05 level.Conclusion: By using the two-step method,using double Pickering emulsion as a template and taking PLGA as a structural material,porous microspheres containing mangiferin were prepared successfully,and the effect of intestinal flora metabolism of mangiferin could be slightly reduced by these porous microspheres. |
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