Preparation Of Hollow Mesoporous Silica Celecoxib Loaded Nanoparticles

Advances and breakthroughs in science and technology have promoted the development of drug delivery systems,among which hollow mesoporous silica(HMS),as an emerging drug carrier,has attracted keen research interest due to its distinct advantages.Celecoxib is a nonsteroidal anti-inflammatory drug that belongs to the BCS Class II.Its unique crystalline structure and special physicochemical properties result in poorly solubility,which makes it a model drug for solubility study.In this study,HMS was synthesized by chemical etching method,and the effects of different amounts of reactants and reaction time on particle size,dispersion properties and orderliness of the final product were explored.Then,the celecoxib-loaded HMS was prepared to investigate the effects of HMS on drug dissolution.Finally,the synthetic HMS was encapsulated by lipid layers to expand the applications of the lipid-coated HMS.The synthetic HMS was characterized by various techniques,including dynamic light scattering(DLS),X-ray diffraction(XRD),and transmission electron microscope(TEM),in order to discuss the effects of reaction conditions(including cetyltrimethylammonium bromide(CTAB),tetraethoxysilane(TEOS),ammonia solution(NH3·H2O),and etching time)on the shell thickness and particle morphology of HMS.The optimal drug-loading method and conditions were determined by comparing the solvent evaporation and maceration-configuration methods.Celecoxib loaded in HMS was characterized by infrared spectrometry,XRD,and differential scanning calorimetry(DSC).A comparative analysis was performed on drug dissolution of HMS and celecoxib-loaded HMS in different media.A novel lipid-coated HMS DDS was established by the film hydration method,and the integrity of the lipid layers was characterized by potentiometry and TEM.According to the above research and analysis,the synthesis conditions of HMS was determined: 0.25 g CTAB,6 m L NH3·H2O,12 m L TEOS,and chemical etching for 16 h.The obtained HMS was highly ordered,uniformly dispersed,and with a diameter of 300 nm.The particle size increased as increasing the amount of CTAB.The shell of HMS became thicker with the addition of TEOS.A larger particle size was observed as the NH3·H2O concentration increased,which caused by the promoted adhesion between HMS particles.Besides,celecoxib was loaded into HMS by solvent evaporation method,and the drug-loading conditions were determined as followed: drug-loading time was 90 min,drug-loading solvent was ethanol,and the ratio between celecoxib and HMS was 2:3.Celecoxib-loaded HMS exhibited a significantly higher drug dissolution rate than celecoxib alone in aqueous solution(containing 0.2% SDS),p H 1.2 hydrochloric acid solution(containing 0.2% SDS)and p H 6.8 phosphate buffer(containing 0.2% SDS).Lipid-coated HMS was successfully prepared by film hydration method.From the study results,it can be concluded that in the process of HMS synthesis by chemical etching,the particle size,dispersion properties,and orderliness of the final product are affected by the amounts of reactants and the etching time;HMS can effectively improve the dissolution rate of celecoxib,providing a reference for the development of poorly soluble drugs.