| Cancer has become one of the diseases with the highest mortality rate,but it is becoming more and more difficult to develop new tumor drugs.Therefore,in order to solve the problem of poor efficacy of a single drug,multiple drugs are often used in combination.Doxorubicin hydrochloride is a hydrophilic broad-spectrum antitumor drug.Curcumin is a fat-soluble drug The combination of the two can reduce the side effects of doxorubicin and produce a synergistic effect.It is difficult for a single carrier to meet the requirements for co-loading drugs with different dissolution properties.Therefore,a“core-shell”structured mesoporous silicon core lipid composite nanocarrier was designed with mesoporous silica as the core to adsorb adriamycin With lipid as the shell,curcumin is loaded.Functional modification of the carrier surface with PEG polymer was carried out to achieve drug co-loading and controlled release with different dissolution properties,providing a theoretical basis for the design and function regulation of drug co-loading systemsIn this dissertation,the W/O/W emulsion was formed by double emulsion method,and the lipid/silicon core nanoparticles were prepared by freeze-drying.The optimal ratio of drug loading was discussed.A modified PEG polymer NH2-PEG3400-COOH was synthesized to modify the surface of the carrier and increase the pH sensitivity of the nanoparticles.The morphology characteristics of the nanoparticles were analyzed by SEM,TEM and particle size analyzer,and the phase characteristics were analyzed by DSC,FT-IR,XRD and BET The dialysis method was used to investigate the nanoparticle release behavior,fit the kinetic model,analyze the nanoparticle release mechanism,and evaluate the stability and antioxidant ability of the sampleAccording to the determination of pharmaceutical properties,for mesoporous silicon core lipid composite nanoparticles,the optimal mass of the drug and the carrier is 1:10,and the encapsulation efficiency and drug loading of doxorubicin are(85.53 ±0.42)%and(4.66±0.02)%,the encapsulation efficiency and drug loading of curcumin were(85.75±0.64)%and(4.75±0.05)%,respectively.After modification,the drug loading performance of the carrier was improved.The encapsulation efficiency and drug loading of doxorubicin were(89.46±0.32)%and(4.71±0.03)%,respectively.The encapsulation efficiency and drug loading of curcumin were(87.21 ±0.19)%and(4.91 ±0.02)%.The size of the nanoparticles before and after the modification is uniform,there is no phenomenon of agglomeration and breakage,and the nanoparticles have better dispersibility and a smaller particle size after modification.By DSC,FT-IR,XRD phase characterization,lipids and mesoporous silicon combine with van der Waals force to form a complex,and NH2-PEG3400-COOH is distributed on the surface of the lipids,resulting in steric hindrance effect.Nitrogen adsorption and desorption experiments further confirmed that the lipid coating on the surface of the mesoporous silicon effectively blocked the mesopores and prevented the drug from leaking from the channels.The in vitro release results of the composite carrier showed that the in vitro release of NH2-PEG3400-COOH modified nanoparticles conformed to a two-way kinetic model,which was a synergistic release of the Fickian diffusion mechanism and the erosion mechanism.NH2-PEG3400-COOH modified nanoparticles are released in simulated tumor cell pH media(pH=6.5～5.5),simulated blood and normal cell pH media(pH=7.4),artificial gastric fluid pH media(pH=1.35)There is a very significant difference in degree(P<0.01),indicating that the carrier has significant pH-sensitive controlled release characteristics and has a sharp response to the pH value of tumor cells.Mesoporous silicon nuclear lipid composite nanoparticles co-loaded with adriamycin and curcumin Later,compared with free drugs,the stability of the drug is improved,as well as its antioxidant activity,which creates conditions for dual drug co-delivery and combined administration. |
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