The Fractal Characteristics Of PH/Temperature Sensitive Mesoporous Hybrid Materials In Drug Delivery Process

In recent years,with the study of mesoporous silica nanoparticle as a drug delivery carrier,smart mesoporous hybrid materials with core-shell structure characteristics have been formed by coating the polymers with pH-or,temperature-sensitivity,photosensitivity on the surface of mesoporous SiO₂,showing a good clinical application prospect.Although the intelligent mesoporous hybrid materials have achieved long-term developments and broad potential applications,their drug-loading capacity and controlled-release mechanism are still unclear,especially the interaction between drug molecules,polymers and mesoporous surface have a great impact on drug loading capacity and controlled release behavior.For these reasons,a series of dual temperature-and pH-responsive nanoparticles and pH-responsive hollow polymer spheres with different shell thickness were prepared so as to explore the influence of shell thickness on the drug delivery system,the evolution of fractal dimension was investigated by small angle X-ray scattering?SAXS?.Thesefore,the research contents mainly included the following aspects:1.The dual?pH-and temperature-?responsive core-shell structured mesoporous nanomaterial P@BMMs with different shell thickness were prepared using bimodal mesoporous silica?BMMs?modified with C=C bond as a core and poly?N-isopropylacrylamide-co-acrylic acid??P?NIPAM-co-AA??copolymer as a shell.At the same time,ibuprofen?IBU?was used as a model drug,the effects of copolymer-coated shell thickness on drug loading and controlled release behavior were investigated by means of SAXS technology.The results showed that with the increase of copolymer-coating time,the nanoparticles still maintained the spherical morphology,and the fractal value increased from 2.02 to 2.12,which proved that the copolymer was gradually wrapped to the surface of BMMs.Meanwhile,the drug loading capacity of nanoparticles increased with the copolymer-coating time,and the fractal dimension was transformed from mass fractal to surface fractal,indicating that IBU was successful loaded into the mesoporous channels.The fractal characteristics of the drug-released samples under different release conditions were transformed from surface fractal to mass fractal,and the drug release rate increased with the increase of the copolymer shell thickness,which proved that the copolymer shell thickness had a certain impact on the drug delivery system,and the drug delivery mechanism following the Korsemeyer-Peppas model.2.Based on the previous work,the dual temperature-and pH-responsive nanoparticles were used as drug carriers,and IBU was used as a model drug for drug loading and releasing behaivors.The effects of nanoparticles on drug loading and controlled release behavior in different external environments?pH/temperature?with different reaction time were investigated by SAXS.The results showed that with the increase of drug loading time,the drug loading capacity of nanoparticles increased firstly and then decreased.At the same time,with the increase of drug releasing time,the drug release rate also increased.3.Using modified dense silica sphere?DNSS?with a particle size of 130 nm as the template,through adjusting the pH-responsive polyacrylic acid?PAA?copolymer-coating time,a series of nano-hybrid microspheres P@SiO₂-MPS with different shell thicknesses were prepared.Then solving the SiO₂ core to obtain the hollow polymer microspheres?HPAA?with different shell thicknesses.Taking IBU as a model drug,SAXS was used to investigate the effect of different copolymer-coating time HPAA on drug loading capacity and release performance in PBS at different pH values?pH 3.0and 7.4?.The results showed that the nanoparticles exhibited surface fractal and the drug-loaded samples still maintained spherical morphology,certified that the drug loading process has no effect on the structure and morphology of HPAA.At the same time,the hollow polymer sphere has a high drug loading capacity,with the increase of copolymer-coating time,the drug loading rate of HPAA also increased.For the drug released performance,the equilibrium release rate of IBU under alkaline conditions was much higher than that under acidic conditions,showing a good pH sensitivity.Moreover,with the increase of the copolymer shell thickness,the release rate also showed a gradually increasing trendency,again proved that the shell thickness has a certain impact on the drug delivery system.Based on the above studies,the crystallization time of the clinoptilolite sol was investigated by SAXS.The results showed that with the increase of crystallization time,the clinoptilolite sol changed from surface fractal to mass fractal and then became to surface fractal again,suggesting that the crystallization time has a certain influence on the clinoptilolite sol.4.In addition to SAXS technique,the application of various characterization methods at the same time,such as X-ray diffraction?XRD?,scanning electron microscopy?SEM?,transmission electron microscopy?TEM?,N₂ sorption isotherms?N₂-sorption?,Fourier transform infrared?FTIR?,thermogravimetric?TG?analysis,dynamic light scattering?DLS?analysis,elemental analysis,ultraviolet visible spectrum?UV-vis?,high performance liquid chromatography?HPLC?on composite nanomaterials and drug delivery system of intelligent materials were used.