关键词: Benzalkonium chloride Eyedrop Human corneal epithelial cell Preservative

Mesh : Humans Preservatives, Pharmaceutical / toxicity Benzalkonium Compounds / toxicity High-Throughput Screening Assays / instrumentation methods Cell Survival / drug effects Dry Eye Syndromes / chemically induced Microfluidic Analytical Techniques / instrumentation Epithelial Cells / drug effects Toxicity Tests / methods instrumentation Drug Evaluation, Preclinical / methods instrumentation Ophthalmic Solutions / toxicity Cell Line Lab-On-A-Chip Devices Epithelium, Corneal / drug effects Cornea / drug effects

来  源:   DOI:10.1016/j.tiv.2024.105843

Abstract:
Traditional experimental methodologies suffer from a few limitations in the toxicological evaluation of the preservatives added to eye drops. In this study, we overcame these limitations by using a microfluidic device. We developed a microfluidic system featuring a gradient concentration generator for preservative dosage control with microvalves and micropumps, automatically regulated by a programmable Arduino board. This system facilitated the simultaneous toxicological evaluation of human corneal epithelial cells against eight different concentrations of preservatives, allowing for quadruplicate experiments in a single run. In our study, the IC50 values for healthy eyes and those affected with dry eyes syndrome showed an approximately twofold difference. This variation is likely attributable to the duration for which the preservative remained in contact with corneal cells before being washed off by the medium, suggesting the significance of exposure time in the cytotoxic effect of preservatives. Our microfluidic system, automated by Arduino, simulated healthy and dry eye environments to study benzalkonium chloride toxicity and revealed significant differences in cell viability, with IC50 values of 0.0033% for healthy eyes and 0.0017% for dry eyes. In summary, we implemented the pinch-to-zoom feature of an electronic tablet in our microfluidic system, offering innovative alternatives for eye research.
摘要:
传统的实验方法在添加到滴眼剂中的防腐剂的毒理学评估中受到一些限制。在这项研究中,我们通过使用微流体装置克服了这些限制。我们开发了一种微流体系统,具有梯度浓度发生器,用于微阀和微泵的防腐剂剂量控制,由可编程的Arduino板自动调节。该系统促进了人角膜上皮细胞对八种不同浓度防腐剂的同时毒理学评估,允许在一次运行中进行四份实验。在我们的研究中,健康眼睛和干眼综合征患者的IC50值差异约为2倍.这种变化可能归因于防腐剂在被培养基洗掉之前保持与角膜细胞接触的持续时间。提示暴露时间在防腐剂细胞毒性作用中的意义。我们的微流体系统,由Arduino自动化,模拟健康和干眼环境,以研究苯扎氯铵的毒性,并揭示细胞活力的显着差异,健康眼睛的IC50值为0.0033%,干眼症的IC50值为0.0017%。总之,我们在微流体系统中实现了电子平板电脑的捏到缩放功能,为眼科研究提供创新的替代方案。
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