Advective drug delivery through the cochlear duct
Friday, April 2, 2021
The cochlea is filled with two lymphatic fluids. The sensory epithelium called the organ of Corti (OoC) separates the two fluids. Corti fluid space, extracellular fluid space within the OoC, is like a slender micro-tube. Substantial potassium ions are constantly released into the Corti fluid through sensory receptor cells. Excess potassium ions in the Corti fluid are resorbed by supporting cells to maintain potassium homeostasis. The release and resorption of potassium inside the Corti fluid along the length of the cochlea exhibit opposing gradients that would render local homeostasis ineffective. Therefore, a longitudinal mixing mechanism should be present to assist the resorption process by reducing the ion concentration gradient.
We hypothesized that mechanical agitations could accelerate the mixing speed of Corti fluid. The motion of fluid particles was obtained by solving the Navier-Stokes equations. The spatiotemporal change of ion concentration was obtained by solving advection-diffusion equation. The propagation speed, wavelength, and vibration amplitude of traveling wave determined the drift (advection) velocity of fluid particles. The amplitude of traveling wave corresponds to the deformation of the enclosing boundary of the Corti fluid, the organ of Corti. Measurements of the organ of Corti deformation show that the active motion of the organ of Corti due to sensory cell’s motility results in larger areal strain compared to the passive cochlea.
The cochlea has remained to this day, virtually inaccessible when it comes to drug delivery. Reliable and controlled delivery to the different parts of the cochlea is a challenging, expensive process. Drug administration at the round window fails to reach the apical region of the cochlea where the fundamental frequencies of the human speech tones are located. Following our hypothesis, one can utilize this intrinsic feature of the Corti fluid to promote drug delivery to different locations along the length of the cochlea.