Evaluation of Sustained-Release Steroid Hydrogels in a Guinea Pig Model for Noise-Induced Hearing Loss

Abstract

The otoprotective effects of thermoreversible poloxamer 407 hydrogels containing dexamethasone or triamcinolone acetonide were evaluated in an animal model of noise-induced hearing loss. Seven days after noise exposure, hearing threshold shifts at 16 kHz were significantly reduced in the 6% dexamethasone group (p < 0.05). Even though no significant differences in hair cell counts were found, histological analysis revealed a significantly higher spiral ganglion cell density in the first turn of the cochlea in this group (p < 0.05). No otoprotective effects were observed after the application of the triamcinolone acetonide hydrogels. As the findings of this study indicate potential otoprotective effects of sustained topical dexamethasone delivery in the setting of noise-induced hearing loss, this strategy merits further evaluation.

Advances and Challenges in Pharmaceutical Therapies to Prevent and Repair Cochlear Injuries From Noise

“…As well, there was significantly higher preserved SGN density in the first turn in the dexamethasone group, suggesting possible protection against supra-threshold ABR amplitude loss (hidden hearing loss). No protection in thresholds or cochlear structures was noted for TAAC (Zhu et al, 2018). A similar lack of threshold protection was seen with 1% dexamethasone hydrogel application 48 h after a 1-h 100 dB SPL noise exposure in guinea pigs (Mamelle et al, 2018).…”

“…No protective effect was noted at any time point utilizing IT injections of dexamethasone sodium phosphate solution (Harrop-Jones et al, 2016). The differing results between these studied utilizing hydrogels may be secondary to differences in drug formulation and noise exposure parameters which induced a larger threshold shift in the Zhu et al (2018) study. Both Zhu et al (2018) and Harrop-Jones et al (2016) noted some protective effect at 7 days after exposure.…”

“…The differing results between these studied utilizing hydrogels may be secondary to differences in drug formulation and noise exposure parameters which induced a larger threshold shift in the Zhu et al (2018) study. Both Zhu et al (2018) and Harrop-Jones et al (2016) noted some protective effect at 7 days after exposure. However, the final time point in Zhu et al (2018) was 28 days and animals were not followed to this time point by Harrop-Jones et al (2016).…”

“…Sustained release using thermoreversible hydrogels as a drug carrier has been shown to increase dexamethasone concentrations and provide lasting exposure in guinea pigs and sheep for days to weeks (Wang et al, 2009, 2011; Borden et al, 2011). However, protective effects have been limited (Yildirim et al, 2005; Harrop-Jones et al, 2016; Mamelle et al, 2018; Zhu et al, 2018). Zhu et al (2018) utilized hydrogels containing 6% dexamethasone or 30% TAAC prior to a 3-h 120 dB SPL noise exposure in guinea pigs.…”

“…However, protective effects have been limited (Yildirim et al, 2005; Harrop-Jones et al, 2016; Mamelle et al, 2018; Zhu et al, 2018). Zhu et al (2018) utilized hydrogels containing 6% dexamethasone or 30% TAAC prior to a 3-h 120 dB SPL noise exposure in guinea pigs. No PTS protection was achieved 28 days after exposure, but a small protective effect was noted at 7 days.…”