Proof of concept of intracochlear drug administration by laser-assisted bioprinting in mice

Abstract

Transtympanic administration is used clinically for the injection of gentamicin and/or corticosteroids. This atraumatic route is based on passive diffusion through the round window membrane (RWM). The main limitation of this method is related to the clearance through the Eustachian tube, making the concentration of the therapeutic agent at the intracochlear level uncertain and limited. Moreover, this technique remains unsuitable for molecules of high molecular weight or in the case of gene therapies. The purpose was to study a new technique of intracochlear administration in an atraumatic, direct and controlled manner by laser-assisted bioprinting (LAB). LAB was used to deliver dexamethasone phosphate with thermosensitive hydrogel on the mouse RWM. After validation of the regularity and homogeneity of the pattern, the diffusion in vivo of the dexamethasone into the perilymph after LAB has been confirmed by ELISA. Auditory function measurements showed no hearing impairment suggesting that bioprinting does not induce significant cochlear damage. Hence, the present proof of concept study introduces a promising approach for inner ear drug delivery.

Keywords: Drug delivery; Hearing loss; Inner ear; Laser-assisted bioprinting.