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.

Nanoparticles‐induced potential toxicity on human health: Applications, toxicity mechanisms, and evaluation models

“…Cheng and Wei showed that therapeutic FAH mRNA delivered by dendrimer‐based lipid NPs normalizes liver function and lengthens survival, via a mouse model of hepatorenal tyrosinemia type I 330 . In an ototoxic mouse model, researchers discovered that dexamethasone‐loaded PLGA NPs delivered by magnetic attraction can prevent hearing loss 368 . Using a mouse model of collagen‐induced arthritis and a human transgenic mouse model of arthritis, Zhang et al 369 .…”

“…330 In an ototoxic mouse model, researchers discovered that dexamethasone-loaded PLGA NPs delivered by magnetic attraction can prevent hearing loss. 368 Using a mouse model of collagen-induced arthritis and a human transgenic mouse model of arthritis, Zhang et al 369 discovered that neutrophil membrane-coated NPs exhibit significant therapeutic efficacy by reducing joint destruction and the severity of arthritis as a whole. There are also studies that examined the antipsoriatic and toxic effects of methotrexate-loaded chitin nanogels in an imiquimod (IMQ)-induced mouse model, and they discovered that they were an ideal delivery platform for topical methotrexate delivery in psoriasis due to their significant antipsoriatic efficacy on IMQ-induced model of psoriasis without any dermal and systemic toxicities.…”

“… 330 In an ototoxic mouse model, researchers discovered that dexamethasone‐loaded PLGA NPs delivered by magnetic attraction can prevent hearing loss. 368 Using a mouse model of collagen‐induced arthritis and a human transgenic mouse model of arthritis, Zhang et al. 369 discovered that neutrophil membrane‐coated NPs exhibit significant therapeutic efficacy by reducing joint destruction and the severity of arthritis as a whole.…”