목적: Dexamethasone is commonly used to treat inner ear disorders, including idiopathic sudden sensorineural hearing loss, through intratympanic (IT) injection. However, its hydrophobic nature limits its permeability through the round window membrane, leading to low drug absorption and rapid clearance from the middle ear. To overcome these limitations, this study developed a dexamethasone nanocrystalline suspension (NS)-embedded hydrogel (NS-G) using a hydroxypropyl methylcellulose (HPMC) polymer. The aim was to enhance cochlear drug delivery, prolong drug retention, and improve therapeutic efficacy against ototoxic hearing loss. 방법:DEX nanocrystals were prepared using a bead-milling technique to achieve submicron-sized particles for improved dissolution and permeability. These nanocrystals were embedded in an HPMC hydrogel matrix to control drug release and prolong residence time in the middle ear. The physicochemical properties of the NS-G system were characterized in terms of particle size, viscosity, and release kinetics. To evaluate cochlear drug delivery, the levels of DEX in cochlear tissue were quantified using LC-MS following IT injection in mice. The therapeutic efficacy of NS-G was assessed in a kanamycin- and furosemide-induced ototoxicity mouse model through auditory brainstem response (ABR) testing and cytokine analysis. 결과:The IT administration of NS-G resulted in significantly higher and more sustained DEX levels in cochlear tissue compared to dexamethasone sodium phosphate (DEX-SP), the conventional water-soluble prodrug. Western blot and immunohistochemistry confirmed improved drug uptake in the cochlea, particularly in the spiral ganglion neurons. In ototoxicity-induced mice, NS-G-treated animals exhibited superior hearing preservation across all tested frequencies (8–32 kHz) compared to saline and DEX-SP-treated groups. Furthermore, NS-G significantly reduced inflammatory cytokine levels, indicating enhanced anti- inflammatory effects. These findings suggest that the nanocrystalline formulation, combined with the HPMC hydrogel, provides better cochlear drug retention and therapeutic efficacy. 결론:The NS-G system effectively enhances cochlear delivery of DEX through IT injection, leading to prolonged drug retention and improved therapeutic outcomes in hearing loss models. The combination of nanocrystal technology and a hydrogel-based delivery system offers a promising strategy for increasing the efficacy of steroid treatment for inner ear disorders. This approach may provide a more efficient and patient-friendly alternative to current IT steroid therapies by reducing drug clearance and enhancing local absorption.