An animal model for continuous drug administration to the inner ear

Abstract

The objectives were to establish an animal model for continuous local drug administration to the inner ear and to present preliminary results on the effect of simple transtympanic installation versus continuous administration of gentamicin on cochlear hair cell loss, using two drug concentrations. A guinea pig model for continuous local drug administration to the inner ear was developed by a posterior tympanotomy and subcutaneous placement of an osmotic micro‐pump fitted with a catheter. The tip of the catheter was fixed in the round window niche. In groups of three animals, gentamicin 0.8–0.84 mg or 3.2–3.36 mg was either installed as a single dose by simple installation in the round window niche through a posterior tympanotomy, or administered continuously over a week by the pump‐catheter system. The animals were sacrificed after a week and hair cell loss determined after dissection and phalloidin‐labelling of the basilar membrane/organ of Corti. Quantitation of cochlear hair cell loss revealed a dose dependent effect of gentamicin. The high dose in both treatment modalities induced a higher percentage of hair cell loss at all distances from the round window membrane, especially towards the cochlear apex. Compared with the single dose transtympanic installation, continuous administration induced a higher hair cell loss close to the round window membrane, but a lower loss towards the apex. The inter‐individual variability of hair cell loss was highest following single dose transtympanic installation. An animal model for continuous local drug administration to the round window membrane and subsequently the inner ear has been established, using the guinea pig and an osmotic micro‐pump/‐catheter. Apart from the given species difference, the model is directly transferable to a pump‐catheter system already used in recent human studies. Cochlear hair cell quantitation showed differentiated morphological damage depending on administration modality, as well as on total gentamicin dose. The variability of morphological damage was higher in transtympanic single dose administration, compared with continuous administration.

• gentamicin
• ototoxicity
• cochlear hair cell loss
• inner ear morphology