Micro CT visualization of silver nanoparticles in the middle and inner ear of rat and transportation pathway after transtympanic injection

Background: Silver nanoparticles (Ag NPs) displayed strong activities in anti-bacterial, anti-viral, and anti-fungal studies and were reportedly efficient in treating otitis media. Information on distribution of AgNPs in different compartments of the ear is lacking. Objective: To detect distribution of Ag NPs in the middle and inner ear and transportation pathways after transtympanic injection. Methods: Contrast effect of Ag NPs in the micro CT imaging was assessed in a phantom. AgNPs at various concentrations (1.85 mM, 37.1 mM, and 370.7 mM) were administered to rat middle ear using transtympanic injection and cadaver heads were imaged using micro CT at several time points. Results: The lowest concentration of Ag NPs that could be visualized using micro CT was 37.1 mM. No difference was observed between the solvents, deionized H<inf>2</inf>O and saline. Ag NPs at 37.1 mM were visible in the middle ear on 7 d post-administration. Ag NPs at 370.7 mM generated signals in the middle ear, ossicular chain, round window membrane, oval window, scala tympani, and Eustachian tube for both 4 h and 24 h time points. A gradient distribution of Ag NPs from the middle ear to the inner ear was detected. The pathways for Ag NPs to be transported from the middle ear into the inner ear are round and oval windows. Conclusion: This study provided the imaging evidence that Ag NPs are able to access the inner ear in a dose-dependent manner after intratympanic administration, which is relevant to design the delivery concentration in the future clinic application in order to avoid adverse inner ear effect.