Transtympanic Injection of Antioxidant-Eluting Microparticles for Otoprotection From Cisplatin Toxicity in a Mouse Model.

Abstract

Cisplatin is a chemotherapeutic agent with the undesirable side effect of ototoxicity. Transtympanic injections of antioxidant formulations may provide local otoprotection. We tested a novel antioxidant-eluting microparticle for its otoprotective capability from systemic cisplatin as measured by cochlear electrophysiology. Basic science. Translational research laboratory. Eighteen mice were assigned to three groups. All mice underwent baseline click-evoked auditory brainstem response (ABR) audiometry and right ear microparticle injections before beginning 42-day intraperitoneal administration regimens of either saline (healthy control empty microparticle [HCEMP] group) or cisplatin (cisplatin empty microparticle [CEMP] group and cisplatin N-acetylcysteine microparticle [CNAC] group). These regimens consisted of three 4-day cycles of intraperitoneal saline or cisplatin administration followed by 10 rest days. HCEMP and CEMP received right-sided transtympanic empty microparticles, and CNAC received transtympanic N-acetylcysteine eluting microparticles. On day 43, all mice underwent posttreatment ABR. ABR thresholds and threshold shifts were analyzed with mixed-effects models and Tukey's post hoc tests and were compared across pretreatment/posttreatment ears, treatment groups, and injected and non-injected ears. We found that threshold shifts in the ears that received a transtympanic injection of N-acetylcysteine and three cycles of intraperitoneal cisplatin were similar to the paired ears of mice that received no cisplatin. Mice that received a transtympanic injection without N-acetylcysteine and intraperitoneal cisplatin had increased thresholds compared to mice that received a transtympanic injection of N-acetylcysteine and cisplatin. Transtympanic N-acetylcysteine microparticle injections provided functional otoprotection in cisplatin-exposed mice.