Insights into the Effect of Nanoconfinement Surface Chemistry on Celecoxib Aggregation and Dissolution by ¹⁹F NMR Spectroscopy

In this study, 19 F solid-state nuclear magnetic resonance (ss-NMR) was applied to explore the effect of pore surface chemical environment on the molecular assembly of celecoxib. Celecoxib, which is hydrophobic, was encapsulated in mesoporous silica modified with different functional groups via the melt-cooling method. The results indicated that mesoporous silica modified with the different functional groups could enhance and regulate the dissolution rate of celecoxib. The 19 F NMR results demonstrated that celecoxib molecules prefer to assemble into liquid-like molecular layers, when confined in the pores modified with hydrophilic functional groups. In contrast, celecoxib molecules embedded in mesoporous silica materials modified with hydrophobic functional groups tend to aggregate in the pore center, forming central amorphous plugs. When different functional groups are modified within the pores, the varying interactions with celecoxib result in different proportions of molecular aggregation states within the pores. Besides that, the dissolution performance of confined celecoxib molecules was determined by the molecular aggregation in the pores. This work uncovers the relationship between surface chemistry and molecular aggregation, which is fundamental to designing porous materials for drug release.