TY  - JOUR
A1  - Kurabi, Arwa
A1  - Pak, Kwang K.
A1  - Bernhardt, Marlen
A1  - Baird, Andrew
A1  - Ryan, Allen F.
T1  - Discovery of a Biological Mechanism of Active Transport through the Tympanic Membrane to the Middle Ear
JF  - Scientific Reports
N2  - 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.
KW  - biological mechanism
KW  - otitis media
KW  - tympanic membrane
KW  - active transport
KW  - middle ear
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167741
VL  - 6
IS  - 22663
ER  - 
TY  - JOUR
A1  - Kurabi, Arwa
A1  - Schaerer, Daniel
A1  - Noack, Volker
A1  - Bernhardt, Marlen
A1  - Pak, Kwang
A1  - Alexander, Thomas
A1  - Husseman, Jacob
A1  - Nguyen, Quyen
A1  - Harris, Jeffrey P.
A1  - Ryan, Allen F.
T1  - Active Transport of Peptides Across the Intact Human Tympanic Membrane
JF  - Scientific Reports
N2  - We previously identified peptides that are actively transported across the intact tympanic membrane (TM) of rats with infected middle ears. To assess the possibility that this transport would also occur across the human TM, we first developed and validated an assay to evaluate transport in vitro using fragments of the TM. Using this assay, we demonstrated the ability of phage bearing a TM-transiting peptide to cross freshly dissected TM fragments from infected rats or from uninfected rats, guinea pigs and rabbits. We then evaluated transport across fragments of the human TM that were discarded during otologic surgery. Human trans-TM transport was similar to that seen in the animal species. Finally, we found that free peptide, unconnected to phage, was transported across the TM at a rate comparable to that seen for peptide-bearing phage. These studies provide evidence supporting the concept of peptide-mediated drug delivery across the intact TM and into the middle ears of patients.
KW  - assay systems
KW  - biological models
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230929
VL  - 8
ER  -