设计和验证定制系统,测量保存在活性存储机中的人类角膜的经皮层电阻抗

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY International Journal of Pharmaceutics: X Pub Date : 2024-02-09 DOI:10.1016/j.ijpx.2024.100234
Marielle Mentek , Benjamin Peyret , Siwar Zouari , Sébastien Urbaniak , Jean-Marie Papillon , Emmanuel Crouzet , Chantal Perrache , Sophie Hodin , Xavier Delavenne , Zhiguo He , Philippe Gain , Gilles Thuret
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引用次数: 0

摘要

角膜上皮屏障是眼部给药的主要限制之一,可以通过评估角膜上皮屏障的电特性对其进行无创探索。储存在主动储存机(ASM)中的人类角膜是探索药物经角膜渗透的有趣生理模型。我们设计了一种适用于保存在 ASM 中的人类角膜的新系统,以探索体内外角膜上皮屏障功能。我们设计了一套双极装置,包括适合角膜 ASM 的 Ag/AgCl 电极适配器和专用软件,并在新鲜切除的猪角膜(n = 59)和在 ASM 中保存 14 天的人角膜(n = 6)上进行了测试。猪角膜在上皮溃疡增大和急性暴露于 0.01% 和 0.05% 苯扎氯铵 (BAC) 的情况下,角膜阻抗呈明显的比例下降。在 ASM 中保存 14 天的人类角膜的角膜阻抗显著增加,这与多层上皮的恢复以及紧密连接标志物 zonula occludens 1、claudin 1 和 occludin 的表达增强有关。这些结果证明了所开发的方法对于探索和开发作为生理药理学模型储存在 ASM 中的人类角膜的相关性。
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Design and validation of a custom-made system to measure transepithelial electrical impedance in human corneas preserved in active storage machine

Corneal epithelial barrier represents one of the major limitations to ocular drug delivery and can be explored non-invasively through the evaluation of its electrical properties. Human corneas stored in active storage machine (ASM) could represent an interesting physiological model to explore transcorneal drug penetration. We designed a new system adapted to human corneas preserved in ASM to explore corneal epithelial barrier function ex-vivo. A bipolar set-up including Ag/AgCl electrodes adaptors to fit the corneal ASM and a dedicated software was designed and tested on freshly excised porcine corneas (n = 59) and human corneas stored 14 days in ASM (n = 6). Porcine corneas presented significant and proportional decrease in corneal impedance in response to increasing-size epithelial ulcerations and acute exposure to benzalkonium chloride (BAC) 0.01 and 0.05%. Human corneas stored 14 days in ASM presented a significant increase in corneal impedance associated with the restoration of a multi-layer epithelium and an enhanced expression of tight junctions markers zonula occludens 1, claudin 1 and occludin. These results support the relevance of the developed approach to pursue the exploration and development of human corneas stored in ASM as a physiological pharmacological model.

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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
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