We propose the use of amine-grafted SBA-15 particles (i.e., APS-SBA-15) for topical delivery of dexamethasone to the eye. Owing to the surface functionalization of amine groups, dexamethasone, an anionic drug, could be effectively loaded in the mesopores of APS-SBA-15 at loading quantities of 68.23 µg/mg to yield DXS@APS-SBA-15, which, in turn, can be released in a sustained manner for 12 h. DXS@APS-SBA-15 exhibited a pronounced mucoadhesive property because of the presence of both amine and hydroxyl groups in the particles. Therefore, when administered to rabbit eyes in vivo, the DXS@APS-SBA-15 appeared to adhere to the mucin and stay longer on the eye surface, where the drug could be released slowly. Hence, DXS@APS-SBA-15 introduced herein showed> 1.8-fold improvement in the in vivo ocular bioavailability of dexamethasone as compared with the conventional eye drop, Maxidex®.