Poly (D ,L -lactide-co-glycolide) (PLGA) particles have been widely used as drug delivery carriers for a variety of payloads. Three forms of dexamethasone (DEX), namely, acetate, base, and phosphate, were incorporated into a PLGA matrix. First, we compared the drug loading efficiency and release kinetics of drug-loaded PLGA particles. Dexamethasone acetate (DEX-Ac) loaded particles exhibited a higher loading efficiency and a more linear release profile of drug as compared with the other forms of DEX particles. Also, we coincorporated oleic acid-coated superparamagnetic iron oxide nanoparticles (SPION) with DEX-Ac into PLGA submicron particles. No differences in size, zeta potential, drug loading, or release kinetics were found between particles prepared with and without SPION. Additionally, particles were applied to an in vitro cochlear, organotypic culture. DEX-Ac PLGA nanoparticles showed a protective effect against 4-hydroxynonenal induced hair cell damage. These results suggest a promising method for inner ear magnetic targeted treatment.