Sara Manjulatha, Chakraborty Sudip, Chen Renxun, Palms Dennis, Katsifis Georgio, Li Zhongyan, Farajikhah Syamak, Massedupally Vinod, Hui Alex, Wong Edgar H H, Kumar Naresh, Vasilev Krasimir, Mackenzie David, Losurdo Linda, Dehghani Farida, Jenssen Havard, Sorensen Kristian, Lin Jennifer S, Barron Annelise E, Willcox Mark
School of Optometry and Vision Science, UNSW Sydney, Australia.
School of Chemistry, UNSW Sydney, Australia.
Exp Eye Res. 2025 Jan;250:110149. doi: 10.1016/j.exer.2024.110149. Epub 2024 Nov 20.
Previous studies have demonstrated that contact lenses coated with the antimicrobial cationic peptide Mel4, a derivative of melimine, can reduce the occurrence of keratitis. However, the antimicrobial activity of Mel4 weakened over time due to its susceptibility to proteolytic degradation. Oligo-N-substituted glycine peptoids such as TM5 and TM18 possess antimicrobial properties and are resistant to proteolytic breakdown. This study focused on exploring methods for covalently attaching these peptoids to contact lenses to enhance their durability and performance in vitro.
The peptoids TM5 and TM18 were covalently attached to etafilcon lenses via carbodiimide chemistry (EDC/NHS), oxazoline plasma, and plasma ion immersion implantation (PIII). The lenses were analysed using X-ray photoelectron spectroscopy (XPS), surface charge, and hydrophobicity. Inhibition of adhesion of multidrug-resistant Pseudomonas aeruginosa and cytotoxicity on corneal epithelial cells were evaluated. The impact of moist heat sterilization on activity was also assessed.
XPS confirmed peptoid binding to lenses. Peptoid coatings slightly increased contact angles (≤23°) without affecting overall charge. Peptoids, bound via carbodiimide, inhibited P. aeruginosa adhesion by over 5 log10 CFU per lens, outperforming melimine, which required six times the concentration for a 3 log10 reduction. Peptoids attached via oxazoline or PIII reduced adhesion by > 5 log10 CFU. All covalent methods significantly reduced bacterial adhesion compared to untreated lenses (P < 0.0001). Peptoid-bound lenses were non-toxic to corneal epithelial cells. Sterilization did not affect carbodiimide-treated lenses but reduced the activity of oxazoline and PIII surfaces by 1-2 log10 CFU.
Peptoids TM5 and TM18 effectively reduced P. aeruginosa adhesion on lenses, with carbodiimide-bound surfaces retaining activity post-sterilization, showing promise for the development of antimicrobial contact lenses.
先前的研究表明，涂有抗菌阳离子肽Mel4（三聚氰胺的衍生物）的隐形眼镜可减少角膜炎的发生。然而，由于Mel4易受蛋白水解降解影响，其抗菌活性会随时间减弱。寡聚N-取代甘氨酸类肽如TM5和TM18具有抗菌特性且抗蛋白水解分解。本研究着重探索将这些类肽共价连接到隐形眼镜上的方法，以提高其体外耐久性和性能。
通过碳二亚胺化学法（EDC/NHS）、恶唑啉等离子体和等离子体离子浸没注入（PIII）将类肽TM5和TM18共价连接到依他氟康隐形眼镜上。使用X射线光电子能谱（XPS）、表面电荷和疏水性对隐形眼镜进行分析。评估多药耐药铜绿假单胞菌的黏附抑制情况以及对角膜上皮细胞的细胞毒性。还评估了湿热灭菌对活性的影响。
XPS证实类肽与隐形眼镜结合。类肽涂层使接触角略有增加（≤23°），而不影响整体电荷。通过碳二亚胺结合的类肽每片隐形眼镜抑制铜绿假单胞菌黏附超过5个对数10CFU，优于三聚氰胺，三聚氰胺需要六倍的浓度才能减少3个对数10。通过恶唑啉或PIII连接的类肽使黏附减少>5个对数10CFU。与未处理的隐形眼镜相比，所有共价方法均显著降低了细菌黏附（P<0.0001）。类肽结合的隐形眼镜对角膜上皮细胞无毒。灭菌不影响碳二亚胺处理的隐形眼镜，但使恶唑啉和PIII表面的活性降低1-2个对数10CFU。
类肽TM5和TM18有效降低了铜绿假单胞菌在隐形眼镜上的黏附，碳二亚胺结合的表面在灭菌后仍保持活性，显示出在抗菌隐形眼镜开发方面的前景。
