Moatti Adele, Silkstone Dylan, Martin Taylor, Abbey Keith, Hutson Kendall A, Fitzpatrick Douglas C, Zdanski Carlton J, Cheng Alan G, Ligler Frances S, Greenbaum Alon
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.
iScience. 2023 May 2;26(6):106789. doi: 10.1016/j.isci.2023.106789. eCollection 2023 Jun 16.
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 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.
将药物疗法输送到内耳以治疗和预防听力损失具有挑战性。全身给药无效，因为只有一小部分治疗剂能到达内耳。通过圆窗膜（RWM）或耳蜗造口术进行注射的侵入性手术可能会对内耳造成损害。另一种方法是通过鼓膜内注射将药物注入中耳，药物主要通过RWM进入内耳。然而，RWM是一个屏障，只对少数分子具有渗透性。为了研究和提高RWM的通透性，我们开发了一种猪RWM模型，其结构和厚度与人类RWM相似。该模型可存活数天，并且可以在多个时间点测量药物通过情况。该模型为开发有效且非侵入性的内耳给药方法提供了一种直接的途径。
