{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T11:06:44Z","timestamp":1778238404572,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,29]],"date-time":"2023-01-29T00:00:00Z","timestamp":1674950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"House Institute Foundation","award":["HIF-121-5"],"award-info":[{"award-number":["HIF-121-5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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\u00ae microbubbles (MBs; VisualSonics\u2014Fujifilm, Amsterdam, The Netherlands) at a concentration of 2 \u00d7 108 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 \u03bcs 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics15020442","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T07:56:48Z","timestamp":1675065408000},"page":"442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Sonoporation of the Round Window Membrane on a Sheep Model: A Safety Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Sandrine","family":"Kerneis","sequence":"first","affiliation":[{"name":"ENT and Cervico-Facial Surgery Department, University Hospital Center of Tours, 2 Boulevard Tonnell\u00e9, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1041-6950","authenticated-orcid":false,"given":"Jean-Michel","family":"Escoffre","sequence":"additional","affiliation":[{"name":"UMR 1253, iBrain, Inserm, Universit\u00e9 de Tours, 10 Boulevard Tonnell\u00e9, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"John J.","family":"Galvin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universit\u00e9 de Tours, 10 Boulevard Tonnell\u00e9, 37000 Tours, France"},{"name":"House Institute Foundation, 2100 W 3rd Street, Suite 111, Los Angeles, CA 90057, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayache","family":"Bouakaz","sequence":"additional","affiliation":[{"name":"UMR 1253, iBrain, Inserm, Universit\u00e9 de Tours, 10 Boulevard Tonnell\u00e9, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3483-7063","authenticated-orcid":false,"given":"Antoine","family":"Presset","sequence":"additional","affiliation":[{"name":"UMR 1253, iBrain, Inserm, Universit\u00e9 de Tours, 10 Boulevard Tonnell\u00e9, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1841-0572","authenticated-orcid":false,"given":"Corentin","family":"Alix","sequence":"additional","affiliation":[{"name":"UMR 1253, iBrain, Inserm, Universit\u00e9 de Tours, 10 Boulevard Tonnell\u00e9, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Oujagir","sequence":"additional","affiliation":[{"name":"UMR 1253, iBrain, Inserm, Universit\u00e9 de Tours, 10 Boulevard Tonnell\u00e9, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Lef\u00e8vre","sequence":"additional","affiliation":[{"name":"UMR 1253, iBrain, Inserm, Universit\u00e9 de Tours, 10 Boulevard Tonnell\u00e9, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5324-2164","authenticated-orcid":false,"given":"Patrick","family":"Emond","sequence":"additional","affiliation":[{"name":"UMR 1253, iBrain, Inserm, Universit\u00e9 de Tours, 10 Boulevard Tonnell\u00e9, 37044 Tours, France"},{"name":"Faculty of Medicine, Universit\u00e9 de Tours, 10 Boulevard Tonnell\u00e9, 37000 Tours, France"},{"name":"Department of Biochemistry and Molecular Biology, University Hospital Center of Tours, 2 Boulevard Tonnell\u00e9, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Blasco","sequence":"additional","affiliation":[{"name":"UMR 1253, iBrain, Inserm, Universit\u00e9 de Tours, 10 Boulevard Tonnell\u00e9, 37044 Tours, France"},{"name":"Faculty of Medicine, Universit\u00e9 de Tours, 10 Boulevard Tonnell\u00e9, 37000 Tours, France"},{"name":"Department of Biochemistry and Molecular Biology, University Hospital Center of Tours, 2 Boulevard Tonnell\u00e9, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Bakhos","sequence":"additional","affiliation":[{"name":"ENT and Cervico-Facial Surgery Department, University Hospital Center of Tours, 2 Boulevard Tonnell\u00e9, 37044 Tours, France"},{"name":"UMR 1253, iBrain, Inserm, Universit\u00e9 de Tours, 10 Boulevard Tonnell\u00e9, 37044 Tours, France"},{"name":"Faculty of Medicine, Universit\u00e9 de Tours, 10 Boulevard Tonnell\u00e9, 37000 Tours, France"},{"name":"House Institute Foundation, 2100 W 3rd Street, Suite 111, Los Angeles, CA 90057, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,29]]},"reference":[{"key":"ref_1","unstructured":"Mathers, C.D., Stein, C., Ma Fat, D., Rao, C., Inoue, M., Tomijima, N., Bernard, C., Lopez, A.D., and Murray, C.J.L. 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