LC–MS Analysis of Dexamethasone Release from Drug-Coated Cochlear Implant Carriers

Despite advances in electrode materials, implantation of cochlear implants (CIs), the primary treatment for severe hearing loss, remains invasive, and the implantation process can result in trauma, inflammation, loss of residual hearing, and vestibular dysfunction. Foreign body reactions may lead to fibrosis, increasing electrode impedance and compromising device performance. As a method of addressing insertion-related trauma, there has been a rising interest in the development of electrode carriers which deliver drugs (for example, dexamethasone, which has demonstrated efficacy in both preclinical and clinical settings) locally. To that end, researchers have investigated a unique coating strategy for the optimization of the perilymphatic concentration-time profile of dexamethasone, and compared it to fully loaded silicone rods, in which the drug is incorporated within the silicone matrix. Silicone rods coated with 1.3 µg, 2.6 µg, or 5.2 µg dexamethasone were implanted into the scala tympani of guinea pigs, and drug concentrations were quantified over 84 days using liquid chromatography-mass spectrometry (LC-MS), while sequential sampling assessed distribution along the scala tympani. A paper based on this work was published in Scientific Reports. ⁽¹⁾

While the implantation of Cis is a common method of treatment for both acquired and congenital profound hearing loss, the procedure remains inherently invasive and may result in insertion trauma. Although there have been advancements in the mechanical design of electrode carriers, progressively reducing the severity of insertion-related damage, surgical manipulation process and mechanical irritation resulting from their implantation still can produce inflammatory responses. ^(2,3) Both the immediate mechanical and subsequent inflammatory effects can lead to the loss of residual low-frequency hearing due to apoptosis of the remaining hair cells in the apical region of the cochlea. ^(4-6) Insertion trauma, over time, can play a part in the degeneration of spiral ganglion neurons throughout the cochlea, which can detrimentally affect CI efficacy due to these neurons constituting the essential interface for electrical signal transduction. ⁽⁷⁾

The researchers reported that the coated rods exhibited an initial burst release, followed by a sustained steady-state phase. The 5.2 µg group peaked at 450 ng/ml, decreasing to 50 ng/ml by day 84. The 2.6 µg group showed a similar profile with proportionally lower levels. Sequential sampling at day 42 after implantation revealed that dexamethasone distributed throughout the length of scala tympani, forming a basal-apical gradient. ⁽¹⁾

“Compared to fully loaded rods,” wrote the authors of the study, ⁽¹⁾ “the coated variants achieved comparable peak concentrations with substantially lower total drug amounts and a prolonged burst phase, which may enhance the suppression of the immediate inflammatory response following implantation. The improved pharmacokinetic efficiency likely also indicates a safer drug exposure profile.”

“To our knowledge,” the authors go on to state, “this is the first study to evaluate silicone dummies loaded with various potentially therapeutic doses of dexamethasone with respect to intracochlear distribution and time course of intracochlear presence in a significant number of animals. The coating strategy used in this study provides an effective method for controlled drug release into the cochlea, with a desired burst release and an optimized concentration-time profile that surpasses silicone drug carriers where the drug is incorporated throughout the entire matrix.” ⁽¹⁾

References

1. Liebau, A.; Kammerer, B.; Kather, M. et al. Long-Term in vivo Pharmacokinetics of Dexamethasone-Loaded Cochlear Implant Electrode Carrier Dummies with Optimized Release Profiles. Sci Rep. 2026. DOI: 10.1038/s41598-026-36620-0
2. Bas, E.; Goncalves, S.; Adams, M. et al. Spiral Ganglion Cells and Macrophages Initiate Neuro-Inflammation and Scarring Following Cochlear Implantation. Front Cell Neurosci. 2015, 9, 303. DOI: 10.3389/fncel.2015.00303
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4. Eshraghi, A. A.; Lang, D. M.; Roell. J. et al. Mechanisms of Programmed Cell Death Signaling in Hair Cells and Support Cells Post-Electrode Insertion Trauma. Acta Otolaryngol. 2015, 135 (4), 328-334. DOI: 10.3109/00016489.2015.1012276
5. Jia, H.; Wang, J.; François, F. et al. Molecular and Cellular Mechanisms of Loss of Residual Hearing after Cochlear Implantation. Ann Otol Rhinol Laryngol. 2013, 122 (1), 33-39. DOI: 10.1177/000348941312200107
6. Kamakura, T.; O'Malley, J. T.; Nadol, J. B. Jr. Preservation of Cells of the Organ of Corti and Innervating Dendritic Processes Following Cochlear Implantation in the Human: An Immunohistochemical Study. Otol Neurotol. 2018, 39 (3), 284-293. DOI: 10.1097/MAO.0000000000001686
7. Khan, A. M.; Handzel, O.; Damian, D. et al. Effect of Cochlear Implantation on Residual Spiral Ganglion Cell Count as Determined by Comparison with the Contralateral Nonimplanted Inner Ear in Humans. Ann. Otol. Rhinol. Laryngol. 2005, 114, 381–385. DOI: 10.1177/000348940511400508