Ultrasound-induced microbubble cavitation via a transcanal or transcranial approach facilitates inner ear drug delivery
Journal
JCI Insight
Journal Volume
5
Journal Issue
3
Date Issued
2020
Author(s)
Abstract
Ultrasound-induced microbubble (USMB) cavitation is widely used to promote drug delivery. 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–printed 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– and 3.7-fold–higher 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. ? 2020, American Society for Clinical Investigation.
Subjects
biotin; fluorescein isothiocyanate; gentamicin; animal experiment; animal tissue; Article; auditory threshold; cell loss; cochlea; cochlear hair cell; controlled study; drug delivery system; external auditory canal; guinea pig; hearing; immunofluorescence; in vitro study; in vivo study; inner ear; male; microbubble; middle ear; nonhuman; safety; skull; ultrasound; ultrasound induced microbubble cavitation; vestibular hair cell
SDGs
Type
journal article