2023 AIChE Annual Meeting
Non-Invasive Delivery of V2O5 Nanowires for the on-Demand Synthesis of Antimicrobials
Otitis media (OM), a prevalent middle ear infection, has been traditionally treated with antibiotics, raising concerns about the rise of antibiotic resistance in children after repeated treatments. The goal is to develop a safe and effective alternative for OM treatment. In previous works, we demonstrated the potent antibacterial properties of vanadium pentoxide nanowires against OM pathogens in a chinchilla animal model, specifically the bacteria Streptococcus pneumoniae. However, the effectiveness of these nanowires is hindered by their inability to penetrate the middle ear non-invasively. Their average size over 400 nm poses a challenge for crossing the eardrum â a barrier that is structurally similar to the skin and impermeable to most molecules. This project aims to confer tissue-penetrating capability to the antibacterial vanadium pentoxide nanowires through the conjugation of select tissue-penetrating peptides. By attaching these peptides to the nanowires, we anticipate the enabling of minimally invasive delivery of the nanowires across the eardrum. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide / N-hydroxysuccinimide (EDC/NHS) crosslinker chemistry was used to conjugate the vanadium nanowire and the membrane-penetrating peptide. The successful crosslinking was analyzed and validated using X-Ray powder diffraction crystallography (XRPD) and Fourier-transform infrared spectroscopy (FTIR). Ex vivo study was performed to examine the membrane-penetrating activity of the peptide-nanowire construct across the eardrum, by infecting the chinchillas (animal model) with OM pathogen and retrieving the bulla bone which contains the ear, to perform time-dependent penetration study of the peptide-nanowire construct. Samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) and other analytical methods. The conjugation of peptides to vanadium pentoxide nanowires represents an innovative approach to address this issue by designing a single-dose, antibiotic-free nanomedicine.