Assessment of drug permeability through an ex vivo porcine round window membrane model

通过离体猪圆窗膜模型评估药物渗透性

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作者: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

Abstract

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.

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