Sonoporation of the Round Window Membrane on a Sheep Model: A Safety Study.

Autor: Kerneis S; ENT and Cervico-Facial Surgery Department, University Hospital Center of Tours, 2 Boulevard Tonnellé, 37044 Tours, France., Escoffre JM; UMR 1253, iBrain, Inserm, Université de Tours, 10 Boulevard Tonnellé, 37044 Tours, France., Galvin JJ 3rd; Faculty of Medicine, Université de Tours, 10 Boulevard Tonnellé, 37000 Tours, France.; House Institute Foundation, 2100 W 3rd Street, Suite 111, Los Angeles, CA 90057, USA., Bouakaz A; UMR 1253, iBrain, Inserm, Université de Tours, 10 Boulevard Tonnellé, 37044 Tours, France., Presset A; UMR 1253, iBrain, Inserm, Université de Tours, 10 Boulevard Tonnellé, 37044 Tours, France., Alix C; UMR 1253, iBrain, Inserm, Université de Tours, 10 Boulevard Tonnellé, 37044 Tours, France., Oujagir E; UMR 1253, iBrain, Inserm, Université de Tours, 10 Boulevard Tonnellé, 37044 Tours, France., Lefèvre A; UMR 1253, iBrain, Inserm, Université de Tours, 10 Boulevard Tonnellé, 37044 Tours, France., Emond P; UMR 1253, iBrain, Inserm, Université de Tours, 10 Boulevard Tonnellé, 37044 Tours, France.; Faculty of Medicine, Université de Tours, 10 Boulevard Tonnellé, 37000 Tours, France.; Department of Biochemistry and Molecular Biology, University Hospital Center of Tours, 2 Boulevard Tonnellé, 37044 Tours, France., Blasco H; UMR 1253, iBrain, Inserm, Université de Tours, 10 Boulevard Tonnellé, 37044 Tours, France.; Faculty of Medicine, Université de Tours, 10 Boulevard Tonnellé, 37000 Tours, France.; Department of Biochemistry and Molecular Biology, University Hospital Center of Tours, 2 Boulevard Tonnellé, 37044 Tours, France., Bakhos D; ENT and Cervico-Facial Surgery Department, University Hospital Center of Tours, 2 Boulevard Tonnellé, 37044 Tours, France.; UMR 1253, iBrain, Inserm, Université de Tours, 10 Boulevard Tonnellé, 37044 Tours, France.; Faculty of Medicine, Université de Tours, 10 Boulevard Tonnellé, 37000 Tours, France.; House Institute Foundation, 2100 W 3rd Street, Suite 111, Los Angeles, CA 90057, USA.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2023 Jan 29; Vol. 15 (2). Date of Electronic Publication: 2023 Jan 29.
DOI: 10.3390/pharmaceutics15020442
Abstrakt: Sonoporation using microbubble-assisted ultrasound increases the permeability of a biological barrier to therapeutic molecules. Application of this method to the round window membrane could improve the delivery of therapeutics to the inner ear. The aim of this study was to assess the safety of sonoporation of the round window membrane in a sheep model. To achieve this objective, we assessed auditory function and cochlear heating, and analysed the metabolomics profiles of perilymph collected after sonoporation, comparing them with those of the control ear in the same animal. Six normal-hearing ewes were studied, with one sonoporation ear and one control ear for each. A mastoidectomy was performed on both ears. On the sonoporation side, Vevo MicroMarker ® microbubbles (MBs; VisualSonics-Fujifilm, Amsterdam, The Netherlands) at a concentration of 2 × 10 8 MB/mL were locally injected into the middle ear and exposed to 1.1 MHz sinusoidal ultrasonic waves at 0.3 MPa negative peak pressure with 40% duty cycle and 100 μs interpulse period for 1 min; this was repeated three times with 1 min between applications. The sonoporation protocol did not induce any hearing impairment or toxic overheating compared with the control condition. The metabolomic analysis did not reveal any significant metabolic difference between perilymph samples from the sonoporation and control ears. The results suggest that sonoporation of the round window membrane does not cause damage to the inner ear in a sheep model.
Databáze: MEDLINE
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