Abstract

Objectives

This study demonstrates a human nasal epithelial mucosa (NEM) on-a-chip integrated with a novel carbon nanofibers-modified carbon (CNFs-C) electrode for real-time quantitative monitoring of in vitro nasal drug delivery. The NEM-on-a-chip was also integrated with platinum electrodes for real-time measurement of transepithelial electrical resistance (TEER) to monitor the epithelial barrier function.

Methods

The air-liquid interface culture of nasal epithelial RPMI 2650 cells in the NEM-on-a-chip was optimized to mimic the key functional characteristics of the human nasal mucosa. The epithelial transport of ibuprofen in the NEM-on-a-chip was electrochemically monitored by the CNFs-C electrode in real-time under static and physiologically realistic dynamic flow conditions.

Results

The proposed NEM-on-a-chip mimics the mucus production and nasal epithelial barrier function comparable to the physiological characteristics of the human nasal mucosa in vivo. The real-time drug quantification by the CNFs-C electrode in the NEM-on-a-chip was similar to measurements produced by the high-performance liquid chromatography method. The drug transport rate monitored in the NEM-on-a-chip was also responsive to the change in the dynamic condition of the fluid in the bottom compartment of the chip, highlighting the importance of emulating the dynamic in vivo condition for nasal drug transport studies.

Conclusion

The proposed novel NEM-on-a-chip with in situ real-time analysis of drug transport and TEER could potentially be used as an in vitro pre-clinical drug screening platform to offer a low-cost and time-efficient alternative to the costly laborious techniques conventionally used for in vitro drug transport assays.

中文翻译：

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通过鼻上皮粘膜片上粘膜模型实时定量监测体外鼻腔给药

摘要

目标

这项研究证明了人类鼻上皮粘膜（NEM）芯片上集成了新型碳纳米纤维修饰碳（CNFs-C）电极，用于实时定量监测体外鼻腔给药。NEM-on-a-chip芯片还集成了铂电极，用于实时测量跨上皮电阻（TEER），以监测上皮屏障功能。

方法

优化了芯片上NEM上鼻腔上皮RPMI 2650细胞的气液界面培养，以模拟人鼻粘膜的关键功能特征。CNFs-C电极在静态和生理上真实的动态流动条件下，实时电化学监测布洛芬在片上NEM的上皮运输。

结果

拟议的芯片上NEM模拟黏液的产生和鼻上皮屏障的功能，可与体内人鼻黏膜的生理特征相媲美。芯片上NEM中CNFs-C电极的实时药物定量与高效液相色谱方法产生的测量结果相似。在片上NEM上监控的药物传输速率也响应于芯片底部隔室中流体动态状况的变化，突出了模拟动态体内状况对鼻部药物传输研究的重要性。

结论

拟议的新型NEM-on-a-a-chip具有药物转运和TEER的原位实时分析功能，可以潜在地用作体外临床前药物筛选平台，从而为昂贵的价格提供低成本和省时的选择传统上用于体外药物转运测定的费力技术。