Inner ear drug delivery via a reciprocating perfusion system in the guinea pig
Inner ear drug delivery via a reciprocating perfusion system in the guinea pig
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DOI：
10.1016/j.jconrel.2005.09.003
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发表时间：
2005-12-10
影响因子：
10.8
通讯作者：
Sewell, WF
中科院分区：
文献类型：
--
作者：
Chen, ZQ;Kujawa, SG;Sewell, WF
在了解与耳蜗神经和听神经退行性变相关的分子机制方面的快速进展，为基因转移和分子方法的发展提供了希望，以治疗这些疾病。为了使基于这些发现的疗法在临床上有用，有必要开发安全可靠的机制，绕过血液迷宫屏障，将药物输送到内耳。为了开发一种供人类使用的内耳灌流装置，开发了一种往复式微流控系统，该系统允许通过基底弯鼓阶的单一入口孔将药物灌流到耳蜗外淋巴中。本文介绍了一种豚鼠体外往复式灌流系统的性能。对灌流后化合物的耳蜗分布的分析利用了沿耳蜗长方向对音调的位置相关反应的产生。用对照的人工外淋巴液灌流没有效果。水杨酸盐(5 MM)和DNQX(6，7-二硝基-2，3-二酮；100和300µM)两种对耳蜗生理学有明显影响的药物，其反应是可逆的。药物效应的大小随着距离灌流吸管10 mm的距离而减小，随剂量和使用时间的延长而增加。(C)2005 Elsevier B.V.保留所有权利。
Rapid progress in understanding the molecular mechanisms associated with cochlear and auditory nerve degenerative processes offers hope for the development of gene-transfer and molecular approaches to treat these diseases in patients. For therapies based on these discoveries to become clinically useful, it will be necessary to develop safe and reliable mechanisms for the delivery of drugs into the inner ear, bypassing the blood-labyrinthine barrier. Toward the goal of developing an inner ear perfusion device for human use, a reciprocating microfluidic system that allows perfusion of drugs into the cochlear perilymph through a single inlet hole in scala tympani of the basal turn was developed. The performance of a prototype, extracorporeal reciprocating perfusion system in guinea pigs is described. Analysis of the cochlear distribution of compounds after perfusion took advantage of the place-dependent generation of responses to tones along the length of the cochlea. Perfusion with a control artificial perilymph solution had no effect. Two drugs with well-characterized effects on cochlear physiology, salicylate (5 mM) and DNQX (6,7-Dinitroquinoxaline-2,3-dione; 100 and 300 mu M), reversibly altered responses. The magnitude of drug effect decreased with distance from the perfusion pipette for up to 10 mm, and increased with dose and length of application. (c) 2005 Elsevier B.V. All rights reserved.