Long-term in vivo pharmacokinetics of dexamethasone-loaded cochlear implant electrode carrier dummies with optimized release profiles

Abstract

Cochlear implants (CIs) are the primary treatment for severe hearing loss. However, despite advances in electrode materials, implantation remains invasive and can cause trauma, inflammation, loss of residual hearing, and vestibular dysfunction. Foreign body reactions may lead to fibrosis, increasing electrode impedance and compromising device performance. To address insertion-related trauma, there is growing interest in developing electrode carriers that deliver drugs locally, such as dexamethasone, which has demonstrated efficacy in both preclinical and clinical settings. This study investigates a novel coating strategy to optimize the perilymphatic concentration–time profile of dexamethasone and compares 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. Drug concentrations were quantified over 84 days using liquid chromatography–mass spectrometry (LC–MS), and sequential sampling assessed distribution along the scala tympani. 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. Compared to fully loaded rods, 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.