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Solid lipid nanoparticles loaded with edaravone for inner ear protection after noise exposure.

Gao G, Liu Y, Zhou CH, Jiang P, Sun JJ - Chin. Med. J. (2015)

Bottom Line: 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.Edaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss (NIHL).

View Article: PubMed Central - PubMed

Affiliation: Center for Otolaryngology of the People's Liberation Army, Naval General Hospital, Beijing 100048, China.

ABSTRACT

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 1 st 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 silvernitrate (AgNO 3 ) 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).

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Related in: MedlinePlus

Changes in hearing threshold, measured using auditory brainstem responses in guinea pigs. The animals were divided into five groups: Noise alone (N, control group, N = 6); noise + iv EDA solution (N + iv sol, N = 18); noise + it EDA solution (N + it sol, N = 18); noise + iv EDA SLNs (N + iv SLNs, N = 18); and noise + it EDA SLNs (N + it SLNs, N = 18). Steady state noise was used for 2 h/d for 4 consecutive days. Data are presented as the mean ± SD, and differences were analyzed with ANOVA for repeated measures (two-way), followed by the Student–Newman–Keuls (SNK) test. SPL was statistically different among the time groups after noise exposure to normal animals and statistically different from the drug administered groups compared to normal animals. The sound pressure level of the intravenous injection of edaravone solution, intratympanic injection of edaravone solution, and intravenous injection of edaravone SLNs group remained elevated, while the intratympanic injection of edaravone SLNs group showed some recovery on day 4 and 6. *P < 0.05, P < 0.01. SLN: solid lipid nanoparticle, EDA: edaravone.
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Figure 1: Changes in hearing threshold, measured using auditory brainstem responses in guinea pigs. The animals were divided into five groups: Noise alone (N, control group, N = 6); noise + iv EDA solution (N + iv sol, N = 18); noise + it EDA solution (N + it sol, N = 18); noise + iv EDA SLNs (N + iv SLNs, N = 18); and noise + it EDA SLNs (N + it SLNs, N = 18). Steady state noise was used for 2 h/d for 4 consecutive days. Data are presented as the mean ± SD, and differences were analyzed with ANOVA for repeated measures (two-way), followed by the Student–Newman–Keuls (SNK) test. SPL was statistically different among the time groups after noise exposure to normal animals and statistically different from the drug administered groups compared to normal animals. The sound pressure level of the intravenous injection of edaravone solution, intratympanic injection of edaravone solution, and intravenous injection of edaravone SLNs group remained elevated, while the intratympanic injection of edaravone SLNs group showed some recovery on day 4 and 6. *P < 0.05, P < 0.01. SLN: solid lipid nanoparticle, EDA: edaravone.

Mentions: The auditory thresholds before noise exposure were essentially equivalent in all of the ears, and there were no significant differences among the groups. Immediately after noise exposure, the average threshold shift was approximately 44 dB SPL. The greatest threshold shift was approximately 50 dB SPL on the 4th day; and at our last observation time point on the 6th day, the ABR threshold still had not recovered to normal and was approximately 50 dB SPL. Noise-induced threshold shifts (TTS), measured 1 day post-noise exposure, were not significantly reduced by treatment with the drug, neither in the local drug delivery groups, in the systematic drug delivery groups, nor in the solution groups or the SLNs groups. NIHL, measured 6 days post-noise, was substantially reduced by treatment with edaravone SLNs administered by intratympanic injection [Figure 1]. Only the edaravone SLNs by local delivery group demonstrated a significant attenuation of the noise-induced threshold shift on the 4th day following exposure.


Solid lipid nanoparticles loaded with edaravone for inner ear protection after noise exposure.

Gao G, Liu Y, Zhou CH, Jiang P, Sun JJ - Chin. Med. J. (2015)

Changes in hearing threshold, measured using auditory brainstem responses in guinea pigs. The animals were divided into five groups: Noise alone (N, control group, N = 6); noise + iv EDA solution (N + iv sol, N = 18); noise + it EDA solution (N + it sol, N = 18); noise + iv EDA SLNs (N + iv SLNs, N = 18); and noise + it EDA SLNs (N + it SLNs, N = 18). Steady state noise was used for 2 h/d for 4 consecutive days. Data are presented as the mean ± SD, and differences were analyzed with ANOVA for repeated measures (two-way), followed by the Student–Newman–Keuls (SNK) test. SPL was statistically different among the time groups after noise exposure to normal animals and statistically different from the drug administered groups compared to normal animals. The sound pressure level of the intravenous injection of edaravone solution, intratympanic injection of edaravone solution, and intravenous injection of edaravone SLNs group remained elevated, while the intratympanic injection of edaravone SLNs group showed some recovery on day 4 and 6. *P < 0.05, P < 0.01. SLN: solid lipid nanoparticle, EDA: edaravone.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837839&req=5

Figure 1: Changes in hearing threshold, measured using auditory brainstem responses in guinea pigs. The animals were divided into five groups: Noise alone (N, control group, N = 6); noise + iv EDA solution (N + iv sol, N = 18); noise + it EDA solution (N + it sol, N = 18); noise + iv EDA SLNs (N + iv SLNs, N = 18); and noise + it EDA SLNs (N + it SLNs, N = 18). Steady state noise was used for 2 h/d for 4 consecutive days. Data are presented as the mean ± SD, and differences were analyzed with ANOVA for repeated measures (two-way), followed by the Student–Newman–Keuls (SNK) test. SPL was statistically different among the time groups after noise exposure to normal animals and statistically different from the drug administered groups compared to normal animals. The sound pressure level of the intravenous injection of edaravone solution, intratympanic injection of edaravone solution, and intravenous injection of edaravone SLNs group remained elevated, while the intratympanic injection of edaravone SLNs group showed some recovery on day 4 and 6. *P < 0.05, P < 0.01. SLN: solid lipid nanoparticle, EDA: edaravone.
Mentions: The auditory thresholds before noise exposure were essentially equivalent in all of the ears, and there were no significant differences among the groups. Immediately after noise exposure, the average threshold shift was approximately 44 dB SPL. The greatest threshold shift was approximately 50 dB SPL on the 4th day; and at our last observation time point on the 6th day, the ABR threshold still had not recovered to normal and was approximately 50 dB SPL. Noise-induced threshold shifts (TTS), measured 1 day post-noise exposure, were not significantly reduced by treatment with the drug, neither in the local drug delivery groups, in the systematic drug delivery groups, nor in the solution groups or the SLNs groups. NIHL, measured 6 days post-noise, was substantially reduced by treatment with edaravone SLNs administered by intratympanic injection [Figure 1]. Only the edaravone SLNs by local delivery group demonstrated a significant attenuation of the noise-induced threshold shift on the 4th day following exposure.

Bottom Line: 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.Edaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss (NIHL).

View Article: PubMed Central - PubMed

Affiliation: Center for Otolaryngology of the People's Liberation Army, Naval General Hospital, Beijing 100048, China.

ABSTRACT

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 1 st 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 silvernitrate (AgNO 3 ) 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).

Show MeSH
Related in: MedlinePlus