Sound Exposure Promotes Intratympanic Drug Delivery to the Inner Ear

Omer J Ungar; Yumai Situ; Jennifer L Spiegel; Joseph M Chen; Vincent Y W Lin; Trung N Le

doi:10.1002/ohn.801

Sound Exposure Promotes Intratympanic Drug Delivery to the Inner Ear

Otolaryngol Head Neck Surg. 2024 Apr 30. doi: 10.1002/ohn.801. Online ahead of print.

Authors

Omer J Ungar^{1

2}, Yumai Situ², Jennifer L Spiegel^{1

2

3}, Joseph M Chen^{1

2}, Vincent Y W Lin^{1

2}, Trung N Le^{1

2}

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
² Biological Sciences Platform, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
³ Department of Otorhinolaryngology, University Hospital, LMU Munich, Munich, Germany.

PMID: 38686601
DOI: 10.1002/ohn.801

Abstract

Objective: To investigate the impact of sound exposure, with the resultant windows vibration on perilymphatic concentrations following intratympanic (IT) dexamethasone and gentamicin in an animal model.

Study design: Animal model blinded study.

Setting: Animal facility of a tertiary medical center.

Methods: Bilateral IT dexamethasone or gentamicin was applied to 15 tested rats. Following injections, each rat was exposed for 3 minutes to free field 30 dB sound pressure level (SPL), 512 vHz noise, with 1 external auditory canal plugged (contralateral control). Following noise exposure, perilymph was obtained from both ears. Drug concentrations were measured using ultrahigh-performance liquid chromatography-mass spectrometer.

Results: For dexamethasone, the average (±SD) perilymphatic steroidal concentration was 0.417 µg/mL (±0.549) in the control ears versus 0.487 µg/mL (±0.636) in the sound-exposed ears (P = .008). The average (±SD) gentamicin perilymphatic concentration was 8.628 µg/mL (±2.549) in the sound-exposed ears, compared to 4.930 µg/mL (±0.668) in the contralateral control (nonsound exposed) ears. Sound exposure promoted steroidal and gentamicin diffusion to the inner ear by an averaged (±SD) factor of 1.431 and 1.730 (±0.291 and 0.339), respectively.

Conclusion: Low-intensity noise (30 dB SPL) was found to enhance dexamethasone phosphate and gentamicin diffusion to the inner ear (by an averaged factor of ∼1.4 and 1.7, respectively) in a murine model.

Keywords: Menière disease; dexamethasone; gentamicin; inner ear pharmacodynamics; intratympanic injection; local drug delivery; steroid; sudden hearing loss.