Comparing round window membrane permeability enhancers: An animal study

Intratympanic (IT) delivery of dexamethasone (DEX) is widely used for treating inner ear disorders; however, its therapeutic efficacy is limited by poor permeability of the round window membrane (RWM). This study aimed to evaluate and compare the efficacy and safety of three pharmacological agents-histamine (HIS), 3% hypertonic saline (3% HS), and sodium caprate (SC)-as adjuvants for enhancing RWM permeability and improving IT-DEX delivery in a murine model. Following IT administration of each permeability enhancer followed by DEX injection, perilymph DEX concentrations were measured using ultra-high-performance liquid chromatography, and DEX receptor expression in the organ of Corti was assessed by immunofluorescence. Structural changes in the RWM were examined by transmission electron microscopy, and auditory function was evaluated using auditory brainstem response (ABR) testing. All three enhancers significantly increased perilymph DEX concentrations compared to controls, with 3% HS demonstrating the highest levels. 3% HS also induced the greatest DEX receptor expression and caused only transient RWM structural alterations without permanent damage. Despite enhanced drug delivery, no statistically significant differences in ABR threshold recovery were observed among treatment groups. These findings demonstrate that 3% HS is the most effective adjuvant among those tested for IT drug delivery, although enhanced inner ear drug penetration does not necessarily translate to improved functional recovery in this model.