목적: In this study, we investigated whether dexamethasone, a hydrophobic drug, can be made into a stable nanosuspension solution, and whether this dexamethasone nanosuspension solution has a higher drug delivery efficiency to cochlea than the hydrophilic dexamethasone sodium phosphate (Dex-SP). 방법:Nanocrystals of dexamethasone were produced by the NUFS (Nanoparticulation using fat and solid lipid) method, a patented method of Biosynectics, inc. Excipients were added to keep nanocrystals suspended in water. Three kinds of nanosuspensions (NUFS A, NUFS B, and NUFS C) were made by varying the composition of this excipient. We examined the safety and efficacy of nanosuspensions in in vitro and in vivo experiments. 결과:The size of dexamethasone nanocrystals in three kinds of nanosuspensions were approximately between 250 and 350 nm. When observed at room temperature for up to 8 hours, all three solutions apparently maintained a suspension state, but the particle size of NUFS C increased to about 1000 nm over time. In the in vitro toxicity assessment, cytotoxicity was not observed when three solutions were treated in HEI-OC1 cell line up to 100 ug/ml. The concentrations of dexamethasone in the perilymph after middle ear drug injection, were examined up to 24 hours, and three groups of nanosuspensions showed significantly higher drug concentration than that of Dex-SP in the result at 6 hours. In addition, interestingly, the concentration of dexamethasone in the tissue of cochlea of NUFS group, was 26-fold higher than that of Dex-SP at 6 hours. In the evaluation of drug efficacy, NUFS B showed better phosphorylation of glucocorticoid receptors than Dex-SP in both in vitro and in vivo, and, in the ototoxic animal model, it showed significantly better hearing protection effect than Dex-SP against ototoxic drugs. In safety evaluation, it showed no toxicity at concentrations up to 20 mg/mL in an in vivo test. 결론:A nanosuspension of dexamethasone was able to deliver dexamethasone to the cochlea very safely and efficiently and showed potential as a formula for intratympanic injection. In addition, it can be applied in studies on the delivery of various hydrophobic antioxidants to treat acute hearing loss.