Abstract
Clinically there is no effective method to prevent drug induced hearing loss in patients undergoing chemotherapy and anti-tuberculosis therapy. In this study, we developed an intratympanic (IT) local drug delivery vehicle featuring hyaluronic acid-based dual viscosity mixture encapsulation of dexamethasone (D), named dual-vehicle + D, and assessed its protective effect in ototoxic hearing loss. We assessed the residence time, biocompatibility, and treatment outcome of the novel vehicle compared with the current standard of care vehicle (saline) and control conditions. The hearing threshold and hair cell count were significantly better in the dual-vehicle + D group compared to the other two groups. The final hearing benefit in the dual-vehicle group was approximately 25–35 dB, which is significant from a clinical point of view. Morphologic evaluation of the cochlear hair cells also supported this finding. Due to the high viscosity and adhesive property of the vehicle, the residence time of the vehicle was 49 days in the dual-vehicle + D group, whereas it was less than 24 h in the saline + D group. There was no sign of inflammation or infection in all the animals. From this study we were able to confirm that dual viscosity mixture vehicle for IT D delivery can effectively block ototoxic hearing loss.
Highlights
Corticosteroid is one of the most widely used medications for various inner ear disorders
The hearing threshold was significantly better in the dual-vehicle + D group than in the saline + D group (p 0.089 at 8 kHz, p 0.012 at 16 kHz, and p < 0.001 at 32 kHz) or the control group (p < 0.001 at 8 kHz, p < 0.001 at 16 kHz, and p < 0.001 at 32 kHz) on post-hearing loss day (PHD) 4
The results from this study showed that IT dexamethasone (ITD) administration via the dual viscosity mixture vehicle is an effective and safe method for preventing ototoxic hearing loss
Summary
Corticosteroid is one of the most widely used medications for various inner ear disorders. Delivering a sufficient amount of steroid over a prolonged duration into the inner ear is not easy. Based on level 2 evidence, the American Academy of Otolaryngology–Head and Neck Surgery has recommended steroid administration as salvage therapy for sudden SNHL (Chandrasekhar et al, 2019). The European Academy of Otology and Neurotology has recommended the use of steroids for the treatment of Meniere’s disease (Magnan et al, 2018). Both systemic and local intratympanic (IT) administration of steroids are associated with considerable challenges.
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