Inner ear is a target for insulin signaling and insulin resistance: evidence from mice and auditory HEI-OC1 cells.

Objective: The mechanisms underlying the association between diabetes and inner ear dysfunction are not known yet. The aim of the present study is to evaluate the impact of obesity/insulin resistance on inner ear fluid homeostasis in vivo, and to investigate whether the organ of Corti could be a target tissue for insulin signaling using auditory House Ear Institute-Organ of Corti 1 (HEI-OC1) cells as an in vitro model.

Methods: High fat diet (HFD) fed C57BL/6J mice were used as a model to study the impact of insulin resistance on the inner ear.

Extracellular Vesicles From Auditory Cells as Nanocarriers for Anti-inflammatory Drugs and Pro-resolving Mediators.

Drug- and noise-related hearing loss are both associated with inflammatory responses in the inner ear. We propose that intracochlear delivery of a combination of pro-resolving mediators, specialized proteins and lipids that accelerate the return to homeostasis by modifying the immune response rather than by inhibiting inflammation, might have a profound effect on the prevention of sensorineural hearing loss. However, intracochlear delivery of such agents requires a reliable and effective method to convey them, fully active, directly to the target cells.

Preliminary Characterization of Extracellular Vesicles From Auditory HEI-OC1 Cells.

Objectives: Isolate, purify, and characterize extracellular vesicles (EVs) obtained from auditory HEI-OC1 cells, and evaluate their suitability for intracochlear transport and delivery of pharmacological drugs and/or pro-resolution mediators of acute inflammatory processes.

Methods: HEI-OC1 EVs were isolated and purified using the exoEasy Maxi Kit, and their size was evaluated by nanoparticle tracking techniques. Bottom-up proteomics of the EVs, either freshly obtained or stored for up to 4 months at -20°C, was performed by LC-ESI-MS/MS.

Prevention of cisplatin-induced hearing loss by extended release fluticasone propionate intracochlear implants.

Objective: Cisplatin is a chemotherapeutic drug known to induce hearing loss. Although corticosteroids may help to mitigate the ototoxic side effects of cisplatin, there are complications associated with their systemic and prolonged use. The goal of this study is to test the efficacy of extended-release fluticasone propionate intracochlear implant particles to protect against cisplatin-induced hearing loss.

A Polymer-Based Extended Release System for Stable, Long-term Intracochlear Drug Delivery.

Objective: Investigate a new polymer-based drug coating suitability for safe intracochlear delivery and ability to maintain long-term physiologically active levels of the corticosteroid fluticasone propionate.

Study Design: In vitro dissolution study to evaluate release profiles of polymer-coated drug particles and in vivo studies using a guinea pig model to measure perilymph drug concentrations at specific time points after implantation with polymer-coated drug particles and evaluate their effect on hearing function.

Methods: Polymer-coated fluticasone propionate (FP) particles were surgically implanted in guinea pigs through the round window membrane into the cochlear scala tympani.