Mastoid approach for local drug delivery to the inner ear for treating hearing loss.

Hearing loss is a prevalent disability worldwide. Dexamethasone (Dex) is commonly used to treat hearing loss, administered either systemically or locally. However, targeted delivery of Dex to the inner ear remains challenging, which limits its therapeutic efficacy. This study aimed to develop new methods to improve Dex delivery to the inner ear and enhance its treatment effect. Mastoid, intraperitoneal, and intratympanic delivery routes for Dex were investigated in guinea pig cochlea. Liquid chromatography-mass spectrometry and immunohistochemistry were employed to compare the distribution of Dex in the perilymph and tissue uptake. Poly (lactic- co -glycolic acid) nanoparticles loaded with Dex (PLGA-NPs-Dex) were prepared, and their transport mechanism across the round window membrane (RWM) was explored. Among the three delivery routes, mastoid administration produced the highest Dex concentration in the perilymph. Compared to the control, PLGA-NPs-Dex provided significantly enhanced protection against lipopolysaccharide- and noise-induced hearing damage following mastoid administration. Mastoid delivery provides an accessible route for drug delivery to the inner ear and nanoparticle-based systems via this route represent a viable strategy for treating inner ear diseases. This approach caused less damage to the inner ear, making it a promising option for clinical use in treating hearing loss. Mastoid approach was a novel method for local drug delivery into the inner ear. PLGA-NPs-Dex showed a significantly better hearing-protective effect against lipopolysaccharides- and noise-induced damages following mastoid delivery. [Display omitted] • Mastoid approach was a novel method for local drug delivery into the inner ear. • Mastoid administration yielded the higher concentration of Dex in the perilymph than the traditional delivery routes. • PLGA-NPs-Dex was prepared and the transport mechanism of it across the round window membrane was studied • PLGA-NPs-Dex showed a better hearing-protective effect against LPS- and noise-induced damages following mastoid delivery. [ABSTRACT FROM AUTHOR]