Abstract
This study was performed to investigate the Eustachian tube as a potential route for contralateral spreading following intratympanic nanoparticle (NP)-conjugated gentamicin injection in a rat model. Sprague–Dawley rats were divided into three groups and substances were injected in the right ear: group 1 (fluorescent magnetic nanoparticles [F-MNPs], n = 4), group 2 (F-MNP-conjugated gentamicin [F-MNP@GM], n = 2), and control group (no injections, n = 2). T2-weighted sequences corresponding to the regions of interest at 1, 2, and 3 h after intratympanic injection were evaluated, along with immunostaining fluorescence of both side cochlea. The heterogeneous signal intensity of F-MNPs and F-MNP@GM on T2-weighted images, observed in the ipsilateral tympanum, was also detected in the contralateral tympanum in 4 out of 6 rats, recapitulating fluorescent nanoparticles in the contralateral cochlear hair cells. Computational simulations demonstrate the contralateral spreading of particles by gravity force following intratympanic injection in a rat model. The diffusion rate of the contralateral spreading relies on the sizes and surface charges of particles. Collectively, the Eustachian tube could be a route for contralateral spreading following intratympanic injection. Caution should be taken when using the contralateral ear as a control study investigating inner-ear drug delivery through the transtympanic approach.
Highlights
This study was performed to investigate the Eustachian tube as a potential route for contralateral spreading following intratympanic nanoparticle (NP)-conjugated gentamicin injection in a rat model
Gentamicin is mostly delivered to the basal turn of the cochlea via the round window, the Eustachian tube in the middle ear is a potential route for the clearance of gentamicin
We observed the temporal and spatial distributions of nanoparticle (NP)-conjugated gentamicin even in the contralateral middle and inner ear following intratympanic injection in a rat model, which led us to hypothesize that the Eustachian tube is a potential route for contralateral spreading
Summary
This study was performed to investigate the Eustachian tube as a potential route for contralateral spreading following intratympanic nanoparticle (NP)-conjugated gentamicin injection in a rat model. We observed the temporal and spatial distributions of nanoparticle (NP)-conjugated gentamicin even in the contralateral middle and inner ear following intratympanic injection in a rat model, which led us to hypothesize that the Eustachian tube is a potential route for contralateral spreading. To the best of our knowledge, no studies have investigated the Eustachian tube as a potential route, previous studies have suggested the possibility of contralateral spreading following intratympanic injection through the connection between the perilymph and cerebrospinal fluid from the cochlear a queduct[5]. We report a previously undescribed potential route, the Eustachian tube, for contralateral spreading following intratympanic NP-conjugated gentamicin injection in a rat model, and discuss the possible underlying mechanism using computational simulations complimented by Multiphysics. The results of our study provide crucial insight into the contraindication of the contralateral ear as a control ear, especially in rat studies investigating inner ear delivery through the transtympanic approach
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