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Our previous study investigated USMB targeting the round window membrane by applying the ultrasound transducer to the tympanic bulla. In the present study, we further extended the use of this technology to enhance drug delivery to the inner ear by introducing the ultrasound transducer into the external auditory canal (EAC) or applying it to the skull. Using a 3-dimensional\u2013printed diffusion apparatus mimicking the pathway for ultrasound passing through and reaching the middle ear cavity in vitro, the models simulating the transcanal and transcranial approach demonstrated 4.8-fold\u2013 and 3.7-fold\u2013higher delivery efficiencies, respectively. In an in vivo model of guinea pigs, by filling tympanic bulla with microbubbles and biotin-FITC, USMB applied transcanally and transcranially induced 2.8-fold and 1.5-fold increases in biotin-FITC delivery efficiencies, respectively. In addition, the gentamicin uptake by cochlear and vestibular hair cells and gentamicin-induced hair cell loss were significantly enhanced following transcanal application of USMB. On the 28th day after transcanal USMB, safety assessment showed no significant changes in the hearing thresholds and the integrity of cochlea. These are the first results to our knowledge to demonstrate the feasibility and support the potential clinical application of applying USMB via EAC to facilitate drug delivery into the inner ear.<\/jats:p>","DOI":"10.1172\/jci.insight.132880","type":"journal-article","created":{"date-parts":[[2020,1,2]],"date-time":"2020-01-02T12:08:48Z","timestamp":1577966928000},"source":"Crossref","is-referenced-by-count":36,"title":["Ultrasound-induced microbubble cavitation via a transcanal or transcranial approach facilitates inner ear drug delivery"],"prefix":"10.1172","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9101-6662","authenticated-orcid":true,"given":"Ai-Ho","family":"Liao","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan."},{"name":"Department of Biomedical Engineering 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