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Title

Novel slow- and fast-type drug release round-window microimplants for local drug application to the cochlea: an experimental study in guinea pigs

Authors
Arnold, Wolfgang
Hennig, Michael
Michaelis, Christiane
Deingruber, Kerstin
Scheler, Renate
Steinhoff, Hans-Joachim
Riphagen, Frits
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Published in Audiology and Neurotology. 2005, vol. 10, no. 1, p. 53-63
Abstract Novel drug release microimplants (0.8 x 1.14 mm; custom-made by Leiras, now Schering OY, Finland) of slow- and fast-release types containing either 0.9 mg beclomethasone or no drug at all were placed unilaterally onto the round-window membrane (RWM) of 45 guinea pigs for a maximum duration of 28 days. The following parameters were tested on days 1, 14 and 28 after implantation: threshold levels of beclomethasone in the perilymph of the scala tympani, auditory brain stem responses (ABR thresholds and ABR threshold shifts), RWM morphology and hair cell loss (cytocochleograms). None of the animals in the non-implanted control group (n = 5) or placebo implant group (n = 15), but all animals in the slow-release-type implant group (n = 15) and fast-release-type implant group (n = 15) revealed the presence of beclomethasone on day 1 (34.9 and 64.3 pg/microl, respectively), day 14 (43.8 and 46.9 pg/microl, respectively) and day 28 after implantation (4.7 and 60.5 pg/microl, respectively). Histology of the RWMs appeared normal, and cytocochleograms revealed no inner hair cell loss and outer hair cell loss within normal ranges (from 0.5 +/- 0.4 to 0.8 +/- 0.2% per cochlea) in both ears in all experimental groups at any time during examination (days 1, 14 and 28). Initial values of ABR thresholds at 3, 6, 9 and 12 kHz did not differ significantly in any of the experimental groups. In non-implanted controls, no significant differences of ABR thresholds were observed in all frequencies tested in either ear on days 1, 14 and 28 compared to initial values, and ABR threshold shifts ranged from -3 +/- 5 dB (min.) to +5 +/- 7 dB (max.). On day 28 after implantation, there were no significant differences of ABR threshold shifts between this and the implant groups, except for 6 kHz of the slow-release device. Therefore, the placebo implants, the slow-release and the fast-release beclomethasone implants appear suitable for further experiments.
Keywords AnimalsBeclomethasone/administration & dosage/pharmacokineticsCochlea/drug effectsDelayed-Action PreparationsDrug ImplantsEvoked PotentialsAuditoryBrain Stem/drug effects/physiologyGlucocorticoids/administration & dosage/pharmacokineticsGuinea PigsInfusionsParenteralMalePerilymph/metabolismRound WindowEar/metabolism
Identifiers
PMID: 15591792
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ARNOLD, Wolfgang et al. Novel slow- and fast-type drug release round-window microimplants for local drug application to the cochlea: an experimental study in guinea pigs. In: Audiology and Neurotology, 2005, vol. 10, n° 1, p. 53-63. doi: 10.1159/000082575 https://archive-ouverte.unige.ch/unige:118016

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Deposited on : 2019-05-22

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