Transtympanic delivery of V2O5 nanowires with a tympanic-membrane penetrating peptide

Abstract

Otitis media is a prevalent pediatric condition. Local delivery of antimicrobial agents to treat otitis media is hindered by the low permeability of the stratum corneum layer in the tympanic membrane. While nanozymes, often inorganic nanoparticles, have been developed to cure otitis media in an antibiotic-free manner in a chinchilla animal model, the tympanic membrane creates an impenetrable barrier that prevents the local and non-invasive delivery of nanozymes. Here, we use a newly developed vanadium pentoxide (V₂O₅) nanowire as an example, which catalyzes the metabolic products of an otitis media pathogen (Streptococcus pneumoniae) into antiseptics, to explore the transtympanic delivery strategies for antimicrobial nanozymes. V₂O₅ nanowires with smaller dimensions (<300 nm in length) were synthesized by optimizing the synthesis conditions. To enhance penetrations across intact tympanic membranes, the nanowire was mixed or surface-modified with a trans-tympanic peptide, TMT3. The peptide-modified nanowires were characterized for their physical properties, catalytic activities, and antimicrobial activities. The cytotoxicity profile and permeation across ex vivo tympanic membrane samples were analyzed for the mixed and surface-modified nanozyme formulations.