Novel Strategies to Improve Cochlear Drug Delivery Using Acoustic Stimulation

Dear Editor,

We wish to highlight an innovative approach that holds promise for enhancing drug distribution within the cochlea, an organ that is notoriously difficult to access and central to hearing loss, the world’s fourth leading cause of disability. Currently, the primary obstacle to effective intratympanic inner ear therapy is the absence of perilymphatic flow within the inner ear, which hinders drug distribution. An emerging method that could address this issue is the use of sound stimulation to induce fluid movement within the cochlea. Ungar et al recently demonstrated that even low-intensity pure-tone stimulation (512 Hz at 30 dB Sound-Pressure Level) improves drug diffusion in the rat cochlea. ¹

These techniques could enable therapeutic agents to reach distant regions of the cochlea more effectively. Drug accumulation in the basal turn reduces absorption through the round window, as the concentration gradient is its main driver. Diffusion of the drug toward the apex would overcome this barrier, thereby increasing the total amount absorbed by the cochlea through the round window. Enhanced drug distribution could improve outcomes for conditions such as sudden sensorineural hearing loss and pave the way for next-generation therapies, including stem cell and gene therapies.

Additionally, 2 techniques have been identified that could further enhance perilymphatic flow. Steady-streaming is a viscosity-dependent phenomenon that occurs during basilar membrane stimulation. While pure-tone stimulation results in isolated vortical flow, an appropriate complex sound could generate a “streaming channel.” Sumner et al demonstrated through computation fluid dynamics simulations that this streaming channel could transport molecules from the basal turn to the cochlear apex along the basilar membrane. ² Another promising method is the use of very low-frequency sounds (4 Hz), which would neither stimulate nor damage the organ of Corti, thus allowing high-intensity sound stimulation (>100 dB). Lukashkin et al demonstrated in an animal model that this approach promotes fluid movement along the cochlea. ³

In summary, sound-induced perilymphatic flow represents a promising new approach for improving drug delivery to the cochlea. We believe this is a priority research topic for inner ear diseases, involving both numerical simulations and animal model experiments.