Advancing Magnetic Nanotechnology For Future Therapies Targeting Inner Ear Conditions

Abstract

Hearing loss (HL) affects more than 5% of the global population, and projections suggest that up to 50% of young people could be affected in the coming years. While most HL cases are linked to local inflammation, treatment options remain limited due to the pro- tective barriers of the inner ear. Intratympanic (ITT) administration is considered the most efficient drug delivery method. Despite this, the round window membrane (RWM) remains a significant barrier for most drugs. Our research seeks to overcome this challenge by us- ing nanotechnology. Specifically, we propose the ITT injection of bio- compatible magnetic nanoparticles (MNPs) loaded with Diclofenac (Dfc) (MNPs@FA.Dfc). These nanoparticles, which we previously developed for this purpose in our research group, will be guided through the RWM into the inner ear using an external magnetic field (EMF). In this study, we modeled the magnetic forces required to pull the MNPs through the RWM at both, short (2 mm) and long dis- tances (2 cm) in a mouse’s head. The amount of MNPs crossing the RWM strongly depends on the applied magnetic force and we found ex vivo that, at short distances (force on one MNP of about 6x10-18 N), 2-3% of the administered MNPs cross the RWM. Additionally, we initiated a concept trial of ITT injection using MNPs in a mu- rine model, performed under anesthesia throughout the procedure. Auditory brain response testing confirmed that MNPs ITT injection and exposure to EMF for 1 hour did not elevate hearing thresholds, maintaining normal values after two months. These results suggest that the eardrum tissue was not compromised due to the injection and healed properly. These findings allow us to conclude that the MNPs can cross the RWM with the adequate design of the EMF, without affecting hearing. The amount of Dfc they can deliver within the inner ear still needs to be determined. The data presented are crucial for future in vivo trials using the developed administration system for therapeutic purposes.