| At present,it is more and more difficult to develop new compounds for original tumor drugs.The design of drug delivery system with two or more drugs delivered at the same time by using the existing tumor drugs and taking the combined drug delivery method has become a new focus of drug delivery system research.Doxorubicin(DOX)and curcumin(CUR)are widely used as antitumor drugs in clinical practice,and synergistic and synergistic effects of curcumin and curcumin were produced under the condition of sequential administration of curcumin before adriamycin.However,doxorubicin is a water-soluble drug,while curcumin is a lipid soluble drug.It is difficult for a single carrier material to carry two drugs with different solubility at the same time,and the sequence release of curcumin and doxorubicin should be achieved.Mesoporous silica nanoparticles are inorganic drug carriers,suitable for loading watersoluble drugs.Lipids are organic carriers,suitable for loading lipid soluble drugs.Combined with the characteristics of mesoporous silica and lipid,and to avoid the defects of both,this paper designed an organic/inorganic material composite carrier with pH-sensitive release characteristics of lipid/mesoporous silicon double-layer structure.Lipid as the outer layer of the composite material,loaded with lipid soluble drug curcumin;the lipid surface is modified by a pH sensitive polymer.Curcumin and doxorubicin were used as model drugs,phospholipids as surfactants,MPEG2000-DSPE as pH sensitive surface modification materials,lipid / curcumin as oil phase,ethanol as cosurfactant,mesoporous silica nanoparticles as the core,dispersed in water phase,and W/O/W emulsion prepared by multiple emulsion method.After freeze drying,coloaded lipid / mesoporous silica composite nanoparticles were prepared.TEM,SEM,FT-IR,DSC,XRD and nanoparticle size analyzer were used to characterize and analyze the morphology,particle size,crystal structure,functional group analysis and thermodynamic properties of the composite nanoparticles.The encapsulation efficiency and drug loading of the composite nanoparticles were determined,and the release behavior and mechanism in vitro were studied to judge the slow release of the composite nanoparticles.Release controlled release behavior,and then explore its antioxidant properties,to understand the composite nanoparticles after modification of its antioxidant effect.According to the determination results of pharmaceutical properties,the drug loading and encapsulation efficiency of adriamycin on unmodified composite nanoparticles were(4.33±0.06%)and(76.28±0.91%).The drug loading and encapsulation efficiency of curcumin were(2.81 ± 0.03%)and(82.47 ± 0.76%)respectively,while the drug loading and encapsulation efficiency of adriamycin on MPEG2000-DSPE modified composite nanoparticles were(3.93±0.04%)and(79.46±0.83%)respectively.The drug loading and encapsulation efficiency of curcumin were(2.33±0.02%)and(78.53±0.69%)respectively.The particle size of unmodified composite nanoparticles is about 338 nm,that of drug-loaded composite nanoparticles modified by MPEG2000-DSPE is about 320 nm,and that of drugloaded nanoparticles modified by MPEG2000-DSPE is about 312 nm.According to the characterization and data analysis of various instruments,the micromorphology of the composite nanoparticles modified by MPEG2000-DSPE is regular spherical,and the particles do not agglomerate and have better dispersion.Phase,crystal form and functional group analysis showed that lipid and silica were coupled.MPEG2000-DSPE was modified on the surface of lipid to form lipid-coated silica core-shell composite carrier.Lipids are crystallized in a mixed crystalline form of α、β and β’,forming a crystal structure with lattice defects.Adriamycin is adsorbed in amorphous state in mesoporous silicon channels,curcumin is dispersed in amorphous state in lattice defects,which improves the stability of double-layer carriers.In vitro release experiments showed that curcumin was released faster than doxorubicin,and doxorubicin was released slowly after lipid disintegration,thus achieving the sequential release of drugs.The compound nanoparticles modified by MPEG2000-DSPE followed a twoway kinetics model in vitro to simulate the pH 6.0 of the stromal fluid of tumors.Diffusion and dissolution played a synergistic role.It had the effect of slow-release and controlled-release.Compared with the unmodified nanoparticles,the drug release rate was higher,showing a significant pH-sensitive trigger release effect,which was conducive to the sensitivity to the microenvironment of tumors.Response.After modification,the composite nanoparticles improve the antioxidant properties of drugs,promote the synergistic effect of curcumin and adriamycin,ensure the stability of drug active molecules in vivo,and show the prospects of future clinical application. |
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