title: Discovery of a Biological Mechanism of Active Transport through the Tympanic Membrane to the Middle Ear.
abstract: Otitis media (OM) is a common pediatric disease for which systemic antibiotics are often prescribed. While local treatment would avoid the systemic treatment side-effects, the tympanic membrane (TM) represents an impenetrable barrier unless surgically breached. We hypothesized that the TM might harbor innate biological mechanisms that could mediate trans-TM transport. We used two M13-bacteriophage display biopanning strategies to search for mediators of trans-TM transport. First, aliquots of linear phage library displaying 10(10th) 12mer peptides were applied on the TM of rats with active bacterial OM. The middle ear (ME) contents were then harvested, amplified and the preparation re-applied for additional rounds. Second, the same naïve library was sequentially screened for phage exhibiting TM binding, internalization and then transit. Results revealed a novel set of peptides that transit across the TM to the ME in a time and temperature dependent manner. The peptides with highest transport capacities shared sequence similarities. Historically, the TM was viewed as an impermeable barrier. However, our studies reveal that it is possible to translocate peptide-linked small particles across the TM. This is the first comprehensive biopanning for the isolation of TM transiting peptidic ligands. The identified mechanism offers a new drug delivery platform into the ME.
authors.affiliation: University of California San Diego, Department of Surgery/Otolaryngology, La Jolla, CA, 92037, USA.
authors.forename: Arwa
authors.initials: A
authors.lastname: Kurabi
authors.affiliation: University of California San Diego, Department of Surgery/Otolaryngology, La Jolla, CA, 92037, USA.
authors.forename: Kwang K
authors.initials: KK
authors.lastname: Pak
authors.affiliation: University of California San Diego, Department of Surgery/Otolaryngology, La Jolla, CA, 92037, USA.|Universitätsklinik Würzburg, Department of ENT, Würzburg, 97070, Germany.
authors.forename: Marlen
authors.initials: M
authors.lastname: Bernhardt
authors.affiliation: University of California San Diego, Department of Surgery/Trauma, La Jolla, CA, 92037, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Baird
authors.affiliation: University of California San Diego, Department of Surgery/Otolaryngology, La Jolla, CA, 92037, USA.|Veterans Affairs San Diego Healthcare System, San Diego, CA, 92161, USA.
authors.forename: Allen F
authors.initials: AF
authors.lastname: Ryan
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D004432:Ear, Middle / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D014432:Tympanic Membrane / Q000378:metabolism*
chemical_list: D010455:Peptides