Protection of Hearing Loss in Ototoxic Mouse Model Through SPIONs and Dexamethasone-Loaded PLGA Nanoparticle Delivery by Magnetic Attraction

Abstract

Background: Ototoxicity currently has no available treatment other than medication withdrawal as soon as toxicity is suspected. The human inner ear organs have little potential for regeneration; thus, ototoxicity-induced hair cell injury is deemed permanent. Dexamethasone (Dexa) is a synthetic steroid analog that has significant potential for otoprotection in the treatment of various inner ear diseases; however, its low absorption into the inner ear prevents significant recovery of function. Nanoparticles facilitate targeted drug delivery, stabilize drug release, and increase half-life of the drug. Methods: This study aimed to develop poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded superparamagnetic iron oxide nanoparticles (SPIONs) and Dexa (PSD-NPs) to control localized drug delivery by magnetic attraction in the treatment of ototoxicity-induced hearing loss. PSD-NPs and without SPIONs (PD-NPs) were prepared using a nanoprecipitation method. Results: Using an inner ear simulating system, we confirmed that PSD-NPs has an otoprotective effect in organotypic culture that is enhanced by magnetic attraction. PSD-NPs delivered via intrabullar injection in a magnetic field penetrated the inner ear and prevented hearing loss progression to a greater degree than equivalent doses of Dexa or PSD-NPs alone (day 28: ototoxic: 80.0 ± 0.0 dB; Dexa 100: 60.0 ± 15.5 dB; PSD 100: 50.0 ± 8.2 dB; PSD 100 with magnet: 22.5 ± 5.0 dB; P < 0.05). The protective effects were confirmed in various in vivo and in vitro models of ototoxicity. Conclusion: Our findings suggest that SPIONs with Dexa and magnetic field application prevent the progression of ototoxicity-induced hearing loss through anti-apoptotic mechanisms in the inner ear. Graphical Abstract: Keywords: superparamagnetic iron oxide nanoparticles, ototoxicity, hearing loss, magnetic attraction, dexamethasone