Background:Antioxidants and the duration of treatment after noise exposure on hearing recovery are important.We investigated the protective effects of an antioxidant substance,edaravone,and its slow-release dosage form,edaravone solid lipid nanoparticles (SLNs),in steady noise-exposed guinea pigs.Methods:SLNs loaded with edaravone were produced by an ultrasound technique.Edaravone solution or edaravone SLNs were administered by intratympanic or intravenous injection after the 1st day of noise exposure.Guinea pigs were exposed to 110 dB sound pressure level (SPL) noise,centered at 0.25-4.0 kHz,for 4 days at 2 h/d.After noise exposure,the guinea pigs underwent auditory brainstem response (ABR) threshold measurements,reactive oxygen species (ROS) were detected in their cochleas with electron spin resonance (ESR),and outer hair cells (OHCs) were counted with silvitrate (AgNO3) staining at 1,4,and 6 days.Results:The ultrasound technique was able to prepare adequate edaravone SLNs with a mean particle size of 93.6 nm and entrapment efficiency of 76.7％.Acoustic stress-induced ROS formation and edaravone exerted a protective effect on the cochlea.Comparisons of hearing thresholds and ROS changes in different animal groups showed that the threshold shift and ROS generation were significantly lower in treated animals than in those without treatment,especially in the edaravone SLN intratympanic injection group.Conclusions:Edaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss (NIHL).