Inorganic/Organic Hybrid Silica Nanoparticles as a Nitric Oxide Delivery Scaffold

The preparation and characterization of nitric oxide (NO)-releasing silica particles formed following the synthesis of N-diazeniumdiolate-modified aminoalkoxysilanes are reported. Briefly, an aminoalkoxysilane solution was prepared by dissolving an appropriate amount of aminoalkoxysilane in a mixture of ethanol, methanol, and sodium methoxide (NaOMe) base. The silane solution was reacted with NO (5 atm) to form N-diazeniumdiolate NO donor moieties on the amino-alkoxysilanes. Tetraethoxy- or tetramethoxysilane (TEOS or TMOS) was then mixed with different ratios of N-diazeniumdiolate-modified aminoalkoxysilane (10 - 75 mol%, balance TEOS or TMOS). Finally, the silane mixture was added into ethanol in the presence of an ammonia catalyst to form NO donor silica nanoparticles via a sol-gel process. This synthetic approach allows for the preparation of NO delivery silica scaffolds with remarkably improved NO storage and release properties, surpassing all macromolecular NO donor systems reported to date with respect to NO payload (11.26μmol·mg^-1), maximum NO release amount (357000 ppb·mg^-1), NO release half-life (253 min), and NO release duration (101 h). The N-diazeniumdiolate-modified silane monomers and the resulting silica nanoparticles were characterized by ²⁹Si nuclear magnetic resonance (NMR) spectroscopy, UV-visible spectroscopy, chemiluminescence, atomic force microscopy (AFM), gas adsorption-desorption isotherms, and elemental analysis.