A Novel Delivery Approach of Clinical Inner Ear Gene Therapy.

Background: To create and develop a delivery approach for clinical inner ear gene therapy, we conducted a study of trans-round window membrane (RWM) microinjection using a pipetting microneedle via transcanal endoscopic ear surgery (TEES).

Methods: The implementation of the trans-RWM microinjection surgery involved seven cadaveric specimens, and the surgical procedures and the pipetting microneedle were developed and optimized. The TEES procedures included tympanic cavity visualization, RWM exposure, stapes footplate perforation, and trans-RWM microinjection. The feasibility of different pipetting microneedles was evaluated during microinjection.

Results: Exposure of the RWM microinjection site could be easily achieved in TEES, and the soft-connected pipetting microneedle was most suitable for the trans-RWM microinjection. The fluid outflow from stapes perforation could be visibly observed during the microinjection, which indicated inner ear drug delivery was successful. This inner ear drug delivery approach was successfully applied in the clinical trial.

Conclusion: The trans-RWM microinjection via the soft-connected pipetting microneedle in TEES was proved to be a feasible delivery approach of the inner ear gene therapy.