A Needle-Free Jet Injection System for Safe and Effective Intratympanic Delivery.

HYPOTHESIS: This study aimed to evaluate the effectiveness of a less invasive drug delivery device, the pyro-drive jet injector-intratympanic (PJI-IT), as an alternative to the conventional intratympanic injection (ITI). BACKGROUND: Conventional ITI using fine needles can cause damage to the tympanic membrane and hearing loss. A safer, less invasive delivery platform would be valuable for the local treatment of inner-ear disorders. METHODS: Lipid nanoparticles (LNPs) containing firefly luciferase (Fluc) mRNA were injected into the middle ears of male guinea pigs (n=30) using the needle-free PJI-IT, which created a small, temporary perforation of the tympanic membrane through a high-pressure liquid jet. Conventional fine [30-gauge (30G)] needle injection was used as control. Perforation size and closure time were measured microscopically. Bioluminescence imaging was performed to evaluate Fluc protein production. Auditory brainstem responses (ABRs) were recorded before and after the injection to assess auditory function. RESULTS: The PJI-IT and the 30G needle provided comparable amounts of Fluc protein in the tympanic cavity and cochlea. Compared with the conventional needle, the PJI-IT caused a smaller perforation of the tympanic membrane, which was closed faster. Auditory function was virtually preserved after injection using the PJI-IT, whereas injection using the conventional fine needle induced significant ABR threshold elevations. CONCLUSIONS: The PJI-IT has the potential to be a safe and minimally invasive instrument for intratympanic injections. The preserved auditory function and rapid healing of the perforated tympanic membrane suggest its clinical availability, especially for the repeated administration of biological agents such as mRNA regenerative medicine.