Drug distribution along the cochlea is strongly enhanced by low-frequency round window micro vibrations

Samuel M. Flaherty, Ian J. Russell, Andrei N. Lukashkin

Research output: Contribution to journalArticlepeer-review

Abstract

The cochlea’s inaccessibility and complex nature provide significant challenges to delivering drugs and other agents uniformly, safely and efficiently, along the entire cochlear spiral. Large drug concentration gradients are formed along the cochlea when drugs are administered to the middle ear. This undermines the major goal of attaining therapeutic drug concentration windows along the whole cochlea. Here, utilizing a well-known physiological effect of salicylate, we demonstrate a proof of concept in which drug distribution along the entire cochlea is enhanced by applying round window membrane low-frequency micro vibrations with a probe that only partially covers the round window. We provide evidence of enhanced drug influx into the cochlea and cochlear apical drug distribution without breaching cochlear boundaries. It is further suggested that ossicular functionality is not required for the effective drug distribution we report. The novel method presented here of local drug delivery to the cochlea could be implemented when ossicular functionality is absent or impeded and can be incorporated in clinically approved auditory protheses for patients who suffer with conductive, sensorineural or mixed hearing loss.

Original languageEnglish
Pages (from-to)1312-1320
Number of pages9
JournalDrug Delivery
Volume28
Issue number1
DOIs
Publication statusPublished - 26 Jun 2021

Bibliographical note

Funding Information:
This work was funded by the Medical Research Council [grant MR/N004299/1].

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords

  • acoustic streaming
  • assisted diffusion in straight pipes
  • cochlea
  • Inner ear drug delivery
  • intratympanic administration
  • round window membrane

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