Preparation Of Temperature-sensitive Mesoporous SiO₂ And Its Fluorescent Performance For Controlled Release Of Ibuprofen

Smart mesoporous hybrid materials with core-shell structural characteristics have been synthesized by coating the polymers（p H and temperature sensitive）on the surface of mesoporous Si O₂,which has high drug loading efficiency and sensitivity to the external environment,showing a good clinical application prospects in the field of sustained and controlled release of drugs.However,the dynamic changes of drug delivery and the drug content at the site of action still cannot be accurately located.Therefore,the introduction of fluorescent molecules into the above-mentioned hybrid material can play a role of real-time monitoring of the drug delivery process and achieve a tracking effect with the help of luminescence.Based on these observations,core-shell structured mesoporous nanomaterial P@BMMs were prepared by using bimodal mesoporous silica（BMMs）modified with C=C bond as a core,poly（N-isopropylacrylamide-co-acrylic acid）[P（NIPAM-co-AA）]copolymer and the fluorescent molecule PID as the shell.ibuprofen（IBU）was used as a model drug,the drug loading and release behavior and its luminescent properties were explored in depth.The main findings are as follows:1.Core-shell mesoporous hybrid materials（P@BMMs）were prepared by one-pot method and two-step method,using the principle of self-assembly,and their morphological characteristics,structural parameters and temperature-sensitive properties were systematically investigated.The results show that the copolymers and fluorescent molecules not only retain the double mesoporous structure of the BMMs after successfully wrapping the surface of the BMMs containing surfactants（CTAB）as shells:worm-like first-order pores around 3 nm and large inter-particles pores around30 nm,possesses a spherical morphology with an average particle size of about 50 nm.Moreover,the phase transition temperature was 29.5℃,which indicates that the synthesized hybrid material still has temperature sensitivity.After the removal of CTAB,the above hybrid materials were loaded as carrier for IBU,and the drug loading reached to 8.49%for one-pot sample and 9.41%for two-step sample.The release results showed that the release rate and equilibrium release amount at 37℃both are higher than 25℃,indicating that the hybrid materials prepared by two different synthesis routes have good temperature sensitivity.Especially with the increase of the amount of fluorescent molecules（PID）,due to the growth of the drug release path,the equilibrium releases of the drug showed a downward trend.At the same time,it was found that there was no significant difference between the different synthesis methods when the amount of fluorescent molecules was less than 7%.However,when the amount of fluorescent molecules was higher than 7%,the equilibrium release amount of the two-step method was higher than that of the one-pot method,indicating that the mesoporous hybrid material prepared by the two-step method is better than the one-pot method.2.The small angle X-ray scattering（SAXS）has been investigated in detail and found that BMMs have typical mass fractal characteristics.The fractal dimension（D_m=2.07）of the BMMs with the encapsulation of polymer and fluorescent molecules in both methods,increased to 2.30 and 2.32 for one-pot and two-step method respectively,indicating that their fractal structure becomes more irregular.It is worth noting that the samples after drug loading all changed from mass fractal to surface fractal,and the surface fractal dimension（D_s）values were 2.92（one-pot method）and2.98（two-step method）.It indicating that the surface became denser and rougher,which further proves the successful loading of the IBU.3.The above synthesized mesoporous hybrid materials prepared by one-pot method and two-step method had a strong fluorescence emission peak near 386 nm after drug loading,which had a significant blue shift compared to PID（466 nm）.The results proved that the fluorescent molecules（PID）existed as a monomer on the surface of the hybrid materials.Fluorescence analysis of the filtrate after drug loading revealed weak fluorescence at 380 nm,indicating that the fluorescent molecules can stably exist on the surface of the porous hybrid material during drug loading.When the added amount of PID is 20%,the self-quenching phenomenon will occur in both samples synthesized by one-pot method and two-step method.Further measurement of the solid sample after release revealed that there was still a fluorescence emission peak near 395 nm.Although a slight red shift occurred compared to before release（380 nm）,the fluorescence intensity of the characteristic peak was significantly enhanced.Additionally,with increasing the amount of PID the fluorescence intensity of the samples synthesized by both synthesis methods become enhanced after release.4.The fractal and particle size changes of P@BMMs during drug loading and release were investigated by SAXS technology.It was found that the surface fractal dimension gradually increased with increasing drug loading time（the D_s value of I/PID-doped P@BMMs-20 increased from 2.27 to 2.92,and the D_s value of I/PID-grafted P@BMMs-20 changed from 2.32 to 2.89）.The particle size also showed an increasing trend,I/PID-doped P@BMMs-20 from 36.7 nm to 43.3 nm,I/PID-grafted P@BMMs-20 from 37.1 nm to 43.4 nm.However,as the release time increases,its fractal dimension returns from surface fractal to mass fractal,and its particle size gradually decreases（I/PID-doped P@BMMs-20 reduced from 41.5 nm to 39.5 nm,and I/PID-grafted P@BMMs-20 from 41.5 nm to 39.4 nm）.The above results indicate that the mesoporous hybrid materials prepared by the one-pot method or two-step method have good fluorescence performance and temperature-sensitive behavior,and can be used as a efficient drug carrier in the field of sustained and controlled release.5.The synthesized composite nanomaterials and samples were characterized after drug loading and release,by various characterization techniques such as X-ray diffraction（XRD）,scanning electron microscopy（SEM）,transmission electron microscopy（TEM）,differential Scanning Calorimetry（DSC）,N₂ sorption isotherms,thermogravimetric analysis（TG）,Fourier transform infrared（FTIR）,ultraviolet spectrum,high performance liquid chromatography（HPLC）,small angle X-ray scattering（SAXS）,photoluminescence spectroscopy（PL）and Steady state/transient fluorescence spectrum（FLS）.