OBJECTIVE: Intratympanic gentamicin injection (ITGI) has gained acceptance worldwide for the treatment of Ménière's disease. Reports assessing the efficacy of ITGI suffer from high variability between patients. This variability may be due to ITGI, which does not permit a sustained diffusion of gentamicin across the round window membrane. The present study investigates the effectiveness of a sustained local hydrogel system on the delivery of gentamicin into the inner ear for the treatment of Ménière's disease. METHODS: A matrix of hydrogel loaded with/without gentamicin was explored in vivo. Gentamicin was applied to the ear of mice either through ITGI or in the hydrogel system. Pharmacokinetics, hearing, and balance function were examined to study how the hydrogel system affected the gentamicin delivery and inner ear functions. RESULTS: The 2 gentamicin delivery methods yielded different kinetics curves. The hydrogel system achieved sustained release during a 7-day period, with a flat plateau phase from Day 1 to Day 3 and slow descent in the subsequent days. The ITGI curve dramatically declined after the peak concentration at Day 1 and was almost eliminated by Day 3. The hydrogel system yielded noticeable balance dysfunction with no significant hearing changes. In contrast, ITGI exhibited no significant influences on the inner ear functions after applying the same dose of 40 kg of gentamicin. CONCLUSION: The hydrogel system established in this research allows for more sustained and consistent and efficient drug release than traditional ITGI for the transport of gentamicin into the inner ear, offering a new and exciting treatment of Ménière's disease.
OBJECTIVE: Intratympanic gentamicin injection (ITGI) has gained acceptance worldwide for the treatment of Ménière's disease. Reports assessing the efficacy of ITGI suffer from high variability between patients. This variability may be due to ITGI, which does not permit a sustained diffusion of gentamicin across the round window membrane. The present study investigates the effectiveness of a sustained local hydrogel system on the delivery of gentamicin into the inner ear for the treatment of Ménière's disease. METHODS: A matrix of hydrogel loaded with/without gentamicin was explored in vivo. Gentamicin was applied to the ear of mice either through ITGI or in the hydrogel system. Pharmacokinetics, hearing, and balance function were examined to study how the hydrogel system affected the gentamicin delivery and inner ear functions. RESULTS: The 2 gentamicin delivery methods yielded different kinetics curves. The hydrogel system achieved sustained release during a 7-day period, with a flat plateau phase from Day 1 to Day 3 and slow descent in the subsequent days. The ITGI curve dramatically declined after the peak concentration at Day 1 and was almost eliminated by Day 3. The hydrogel system yielded noticeable balance dysfunction with no significant hearing changes. In contrast, ITGI exhibited no significant influences on the inner ear functions after applying the same dose of 40 kg of gentamicin. CONCLUSION: The hydrogel system established in this research allows for more sustained and consistent and efficient drug release than traditional ITGI for the transport of gentamicin into the inner ear, offering a new and exciting treatment of Ménière's disease.
Authors: Mohammad N Kayyali; Julian R A Wooltorton; Andrew J Ramsey; Mei Lin; Tiffany N Chao; Andrew Tsourkas; Bert W O'Malley; Daqing Li Journal: J Control Release Date: 2018-04-16 Impact factor: 9.776