목적: Glucocorticoids are widely used to treat various inner ear diseases. In particular, for patients with idiopathic sudden sensorineural hearing loss, glucocorticoids are the first-line therapy, and intratympanic (IT) steroid injection is used for patients who experience incomplete recovery from hearing loss within two to six weeks after symptom onset. However, effective drug delivery into the inner ear remains a significant challenge. Dexamethasone palmitate (DP) is encapsulated in solid lipid nanoparticles composed of palmitic acid and has hydrophobic properties due to its chemical structure. Its hydrophobic nature differs from the hydrophobicity of conventionally used dexamethasone sodium phosphate (DSP). Due to this difference, DP is expected to enhance drug delivery efficacy when administered intratympanically. To evaluate its protective effect on hair cells, ex vivo studies were conducted to assess DP’s effectiveness against ototoxicity induced by kanamycin sulfate. 방법: P3 ICR mice were sacrificed, and cochleae were harvested and incubated. Kanamycin sulfate, a known ototoxic agent, was administered 24 hours after incubation. DP and DSP were administered either 24 hours before or simultaneously with kanamycin sulfate. 24 hours after kanamycin sulfate administration, the cochleae were stained, and surviving hair cells were counted. Surviving hair cells were defined as those stained with both myosin VIIa and phalloidin. The number of hair cells was counted from three regions of the cochleae: apex, middle, and basal turn. 결과: In the ex vivo experiment, 7 mM kanamycin sulfate induced significant hair cell damage. In the apex region of the cochlea, both DP- and DSP-treated cochleae showed protective effect against kanamycin sulfate. DP-treated cochleae showed a higher number of surviving outer hair cells when administered 24 hours before kanamycin sulfate (53 outer hair cells/100µm in DP-treated cochleae and 35 outer hair cells/100µm for DSP-treated cochleae). In the middle turn, DP-treated cochleae showed a higher number of surviving hair cells, especially outer hair cells, when administered simultaneously with kanamycin sulfate (18 outer hair cells/100µm in DP-treated cochleae vs. 8 outer hair cells/100µm for DSP-treated cochleae). In the basal region, neither DP- and DSP- demonstrated a notable protective effect. 결론: In our ex vivo experiment, DP exhibited a protective effect against kanamycin sulfate-induced ototoxicity that was comparable to or greater than that of DSP. These differences may be attributed to the hydrophobic properties of DP. DSP is known to protect against hair cell damage caused by ototoxic agents. Its proposed protective mechanism involves inhibiting the mitochondrial apoptotic pathway and suppressing tumor necrosis factor- α, resulting in anti-apoptotic and anti-inflammatory effects. To investigate the mechanisms behind these differences, further in vitro studies are required to evaluate the drug’s mode of action. Additionally, in vivo experiments are necessary to confirm DP’s efficacy in improving drug delivery into the inner ear.