Construction Of Drug Carriers Based On Porous Silicon Matrix Composites And Their Sustained Release Properties

With its unique properties,porous silica-based materials have shown broad application prospects in many fields.At present,important progress has been made in catalytic and controlled release systems based on amino functionalized mesoporous silica.With the development of mesoporous silica controlled release system,functionalized mesoporous materials will be more widely used in medicine.Therefore,it is of great significance to study and construct a drug controlled release carrier with the ability to sense and respond to human physiological stimulation signals.In this paper,the amino functionalized SBA-16 composite（NH₂-SBA-16）was first prepared by post-synthesis and grafting using ethyl orthosilicate（TEOS）and3-aminopropyl triethoxysilane（APS）as raw materials,and then NH2-SBA-16 was used as a carrier.The post-synthetic encapsulation technology was used to encapsulate the drug indomethacin（IMC）by solution diffusion adsorption.Finally,the ph-responsive drug-loaded silicon composites（NH₂-SBA-16@IMC@GA）and magnetically responsive drug-loaded silicon composites（NH₂-SBA-16@FIG）were prepared by gelatin-glutaraldehyde condensation and cross-linking technology.Finally,the properties of Knoevenagel condensation reaction and controlled drug release of the three composites were investigated.The main contents include:（1）Preparation and catalytic properties of amino functionalized SBA-16 compositesAminopropyl functionalized SBA-16（NH₂-pr-SBA-16）was prepared by post-synthesis and grafting using triblock copolymers P123 and F127 as mixed template agents,ethyl orthosilicate（TEOS）and 3-aminopropyl triethoxysilane（APS）as raw materials.X-ray powder diffraction,N₂adsorption-desorption isotherm,pore size distribution and electron microscope analysis showed that the amino-propyl functionalized SBA-16 still had ordered three-dimensional cubic mesoporous structure and high specific surface area.Infrared spectroscopy and ¹³C solid state NMR analysis showed that the surface of the carrier SBA-16 was successfully functionalized with amino groups.The catalytic properties of x NH₂-pr-SBA-16 series composites was studied by Knoevenagel condensation reaction of benzaldehyde and malonitrile.The Knoevenagel condensation reaction process was studied by the second order rate equation model and the kinetic model was verified.After 5 cycles,0.2NH₂-pr-SBA-16 still maintained high catalytic activity against benzaldehyde and malonitrile,and its catalytic active sites could be well preserved.（2）Preparation and sustained-release properties of ph-responsive drug-loaded silicon matrix compositesThe ordered mesoporous silica SBA-16 was used as the carrier,3-aminopropyl triethoxysilane（APS）as the silane coupling agent,indomethacin（IMC）as the drug loading center,and glutaraldehyde condensation of cross-linked gelatin condensation polymer（GA）as the coating agent.A ph-responsive gelatin-coated amino-modified drug-loaded composite（NH₂-SBA-16@IMC@GA）was prepared by post-synthetic encapsulation technology.Through various characterization techniques,it was proved that the drug IMC was adsorbed by mesoporous material NH₂-SBA-16 in NH₂-SBA-16@IMC@GA drug-loaded composite material,and its structure was preserved.Subsequently,the polymer was uniformly and densely wrapped around NH₂-SBA-16@IMC material by the condensation of gelatin and glutaraldehyde crosslinked polymer.The in vitro release properties of Ph-responsive drug-loaded silicon matrix composites NH₂-SBA-16@IMC@GA were simulated under 37±1℃and different media（p H 2.0,6.8 and 7.4,respectively）.The results showed that the drug-loaded composite could release in response to p H environment,and the release rate of the drug can be effectively controlled.In vitro release studies,the release amounts of NH₂-SBA-16@IMC@GA composite at three different p H environments were 5%,41%and 86%,respectively,proving that it has a certain p H responsiveness.When p H=7.4,the drug release rate of NH₂-SBA-16@IMC@GA was 21.0%at 6 h and 86%at 72 h.The composite material had high drug loading capacity and long sustained release time.The results showed that the release process of NH₂-SBA-16@IMC@GA was consistent with the first-order drug release equation and the Higuchi plane diffusion model equation.（3）Preparation and sustained-release properties of magnetic ph-responsive drug-loaded silicon matrix compositesThe magnetic drug-loading precursor NH₂-SBA-16@FI was prepared by solution diffusion adsorption method with SBA-16 as the carrier,Fe₃O₄ as the magnetic nanoparticles,APS as the silane coupling agent,and IMC as the drug loading center.Subsequently,a magnetic ph-responsive drug-loaded composite（NH₂-SBA-16@FIG）was prepared by coating NH₂-SBA-16@FI with a condensation polymer of glutaraldehyde condensed and cross-linked gelatin.The in vitro simulated drug release properties of magnetic NH₂-SBA-16@FIG drug-loaded composites was investigated at 37℃and three p H values（2.0,6.8 and 7.4）.IMC was used as the model drug to study the drug loading ability of the magnetic composite,and the drug concentration was optimized during the drug loading process.The ph-responsive drug release ability of the drug-loaded system was confirmed by in vitro drug release experiments in a simulated tumor environment.The biocompatibility of the magnetic drug-loaded composite materials(NH_2-SBA-16@FIG)and the cytotoxicity of the magnetic drug-loaded composite materials（NH₂-SBA-16@FIG）in vitro were evaluated by cytotoxicity experiments.The results showed that the drug-loaded complex was responsive to colon p H environment and could effectively control the release rate of IMC。The release process of the magnetic drug-loaded composite NH₂-SBA-16@FIG conforms to the first-order drug release equation and the Higuchi planar diffusion mode equation.