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人体尸体原位鼓膜和圆窗膜药物渗透特性评估

An Evaluation of the Drug Permeability Properties of Human Cadaveric In Situ Tympanic and Round Window Membranes.

作者信息

Veit Joachim G S, Birru Bhaskar, Wang Yong, Singh Ruby, Arrigali Elizabeth M, Park Ryan, Miller Briggs, Firpo Matthew A, Park Albert H, Serban Monica A

机构信息

Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA.

Montana Biotechnology Center (BIOTECH), University of Montana, Missoula, MT 59812, USA.

出版信息

Pharmaceuticals (Basel). 2022 Aug 23;15(9):1037. doi: 10.3390/ph15091037.

Abstract

It is estimated that hearing loss currently affects more than 1.5 billion people, or approximately 20% of the global population; however, presently, there are no Food and Drug Administration-approved therapeutics or prophylactics for this condition. While continued research on the development of otoprotective drugs to target this clear unmet need is an obvious path, there are numerous challenges to translating promising therapeutic candidates into human clinical testing. The screening of promising drug candidates relies exclusively on preclinical models. Current models do not permit the rapid high-throughput screening of promising drug candidates, and their relevance to clinical scenarios is often ambiguous. With the current study, we seek to understand the drug permeability properties of the cadaveric tympanic and round window membranes with the goal of generating knowledge that could inform the design and/or evaluation of in vitro organotypic models. The development of such models could enable the early high-throughput screening of topical therapeutic candidates and should address some of the limitations of currently used animal models.

摘要

据估计,目前听力损失影响着超过15亿人,约占全球人口的20%;然而,目前美国食品药品监督管理局尚未批准针对这种情况的治疗方法或预防措施。虽然继续研究开发针对这一明显未满足需求的耳保护药物是一条显而易见的途径,但将有前景的治疗候选药物转化为人体临床试验存在诸多挑战。筛选有前景的药物候选物完全依赖于临床前模型。当前的模型不允许对有前景的药物候选物进行快速高通量筛选,而且它们与临床情况的相关性往往不明确。通过本研究,我们试图了解尸体鼓膜和圆窗膜的药物渗透特性,目的是获取能够为体外器官型模型的设计和/或评估提供信息的知识。开发这样的模型可以实现对局部治疗候选物的早期高通量筛选,并应解决当前使用的动物模型的一些局限性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff57/9501436/00b4ddd819f5/pharmaceuticals-15-01037-g001.jpg

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