School of Engineering , University of Liverpool , Brownlow Hill , Liverpool L69 3GH , United Kingdom.
Institute of Ageing and Chronic Diseases Department of Eye and Vision Science , University of Liverpool , Apex Building, West Derby Street , Liverpool L7 8TX , United Kingdom.
ACS Appl Mater Interfaces. 2019 Oct 16;11(41):37491-37501. doi: 10.1021/acsami.9b13958. Epub 2019 Oct 2.
Microbial keratitis is a serious sight threatening infection affecting approximately two million individuals worldwide annually. While antibiotic eye drops remain the gold standard treatment for these infections, the significant problems associated with eye drop drug delivery and the alarming rise in antimicrobial resistance has meant that there is an urgent need to develop alternative treatments. In this work, a nitric oxide releasing contact lens gel displaying broad spectrum antimicrobial activity against two of the most common causative pathogens of microbial keratitis is described. The contact lens gel is composed of poly-ε-lysine (pεK) functionalized with nitric oxide (NO) releasing diazeniumdiolate moieties which enables the controlled and sustained release of bactericidal concentrations of NO at physiological pH over a period of 15 h. Diazeniumdiolate functionalization was confirmed by Fourier transform infrared (FTIR), and the concentration of NO released from the gels was determined by chemiluminescence. The bactericidal efficacy of the gels against and was ascertained, and between 1 and 4 log reductions in bacterial populations were observed over 24 h. Additional cell cytotoxicity studies with human corneal epithelial cells (hCE-T) also demonstrated that the contact lens gels were not cytotoxic, suggesting that the developed technology could be a viable alternative treatment for microbial keratitis.
微生物角膜炎是一种严重的威胁视力的感染，全球每年约有 200 万人受到影响。虽然抗生素眼药水仍然是这些感染的黄金标准治疗方法，但与眼药水药物输送相关的重大问题以及抗菌药物耐药性的惊人上升意味着迫切需要开发替代治疗方法。在这项工作中，描述了一种释放一氧化氮的隐形眼镜凝胶，该凝胶对微生物角膜炎的两种最常见的病原体具有广谱抗菌活性。隐形眼镜凝胶由聚-ε-赖氨酸（pεK）组成，用释放一氧化氮（NO）的 diazeniumdiolate 部分功能化，使其能够在生理 pH 值下持续释放杀菌浓度的 NO，持续时间为 15 小时。Diazeniumdiolate 功能化通过傅里叶变换红外（FTIR）得到证实，通过化学发光法确定凝胶中释放的 NO 浓度。凝胶对 和 的杀菌效果进行了测定，在 24 小时内观察到细菌数量减少了 1 到 4 个对数级。与人角膜上皮细胞（hCE-T）的进一步细胞毒性研究也表明隐形眼镜凝胶没有细胞毒性，这表明开发的技术可能是治疗微生物角膜炎的可行替代方法。
