Assessment of drug permeability through an ex vivo porcine round window membrane model
Adele Moatti,
Dylan Silkstone,
Taylor Martin,
Keith Abbey,
Kendall A Hutson,
Douglas C Fitzpatrick,
Carlton J Zdanski,
Alan G Cheng,
Frances S Ligler,
Alon Greenbaum
Affiliations
Adele Moatti
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27606, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27606, USA
Dylan Silkstone
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27606, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27606, USA
Taylor Martin
Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27606, USA; Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27606, USA
Keith Abbey
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27606, USA
Kendall A Hutson
Department of Otolaryngology- Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Douglas C Fitzpatrick
Department of Otolaryngology- Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Carlton J Zdanski
Department of Otolaryngology- Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Alan G Cheng
Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA 94305, USA
Frances S Ligler
Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA
Alon Greenbaum
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27606, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27606, USA; Corresponding author
Summary: Delivery of pharmaceutical therapeutics to the inner ear to treat and prevent hearing loss is challenging. Systemic delivery is not effective as only a small fraction of the therapeutic agent reaches the inner ear. Invasive surgeries to inject through the round window membrane (RWM) or cochleostomy may cause damage to the inner ear. An alternative approach is to administer drugs into the middle ear using an intratympanic injection, with the drugs primarily passing through the RWM to the inner ear. However, the RWM is a barrier, only permeable to a small number of molecules. To study and enhance the RWM permeability, we developed an ex vivo porcine RWM model, similar in structure and thickness to the human RWM. The model is viable for days, and drug passage can be measured at multiple time points. This model provides a straightforward approach to developing effective and non-invasive delivery methods to the inner ear.
