Here we present an efficient, quick, and simple method of cochlear pumping, through large-amplitude, low-frequency reciprocal oscillations of the stapes and round window, which can consistently and uniformly deliver drugs along the entire length of the intact cochlea within minutes without disrupting the cochlear boundaries. The method should facilitate novel ways of approaching the treatment of inner ear disorders because it overcomes the challenge of delivering therapeutics along the entire cochlear length.
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A large number of methods, including intracochlear administration, cochleostomy, and canalostomy, have been proposed for solving the problem of uniform drug distribution along the cochlea, but only two current strategies address this problem without breaching the boundaries of the intact cochlea (e.g., see El Kechai et al., 2015). The first strategy relies on retaining drugs in contact with the RW to allow drug diffusion into the cochlear apex. Notable examples of devices designed for this purpose include microwicks, osmotic pumps, etc. Hydrogel-based drug delivery systems also allow retention of therapeutics in the middle ear in contact with the RW. The problem with this strategy is that retention of drugs at the RW leads to their establishing steady-state concentration gradients along the cochlea, which depend on the relationship between diffusion and clearing (Salt and Ma, 2001, Sadreev et al., 2019), but the base-to-apex gradients can still be very pronounced.
The second strategy, although relatively non-invasive to the cochlea, requires development of more complex drug formulations. The technique employs drug-loaded nanoparticles, which could be used to take advantage of the anatomical and cellular features of the cochlea, which enable drug uptake through routes and pathways other than the ST route (Buckiová et al., 2012, Glueckert et al., 2018). Magnetically driven, drug-loaded magnetic nanoparticle can also be actively distributed along the entire cochlea (Ramaswamy et al., 2017).
Here we demonstrate that cochlear pumping (CP), through pressure oscillations in the ear canal at frequencies low enough to avoid damage to the cochlear sensory apparatus, can consistently and uniformly deliver drugs along the entire length of the intact cochlea within minutes without disrupting the cochlear boundaries.