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具有双氯芬酸洗脱能力的低摩擦水凝胶用于干眼症治疗隐形眼镜。

Low friction hydrogel with diclofenac eluting ability for dry eye therapeutic contact lenses.

作者信息

Silva Diana C, Oliveira Margarida, Marto-Costa Carolina, Teixeira João, Oom Madalena Salema, Pinto Carlos A, Saraiva Jorge A, Marques Ana Clara, Fitzhenry Laurence, Serro Ana Paula

机构信息

Centro de Química Estrutural (CQE), Institute of Molecular Sciences, Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal; Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, 2829-511 Caparica, Almada, Portugal.

Centro de Química Estrutural (CQE), Institute of Molecular Sciences, Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.

出版信息

Methods. 2025 Feb;234:67-84. doi: 10.1016/j.ymeth.2024.11.015. Epub 2024 Nov 29.

DOI:10.1016/j.ymeth.2024.11.015
PMID:39617282
Abstract

When placed in the eye, contact lenses (CLs) disturb the tear fluid and affect the natural tribological behaviour of the eye. The disruption in the contact mechanics between the ocular tissues can increase frictional shear stress and ocular dryness, causing discomfort. Ultimately, continuous CLs wear can trigger inflammation which is particularly critical for people suffering from dry eye. In this work, a double strategy was followed to obtain therapeutic daily disposable CLs for dry eye: a hydroxyethyl methacrylate (HEMA) based hydrogel was coated with two natural polysaccharides, chitosan (CHI) and hyaluronic acid (HA) and posteriorly loaded with an anti-inflammatory drug (diclofenac, DCF). Material sterilisation was carried out by high hydrostatic pressure (HHP) combined with moderate temperature. The friction coefficient (μ) was determined in the presence of different tear biomolecules (cholesterol, lysozyme and albumin) using a nanotribometer. Drug release experiments were performed in static and in hydrodynamic conditions. The material was extensively characterised, regarding surface morphology/topography, optical properties, water content and swelling behaviour, wettability, ionic and oxygen permeability and mechanical properties. It was found that the coating did not impair the physico-chemical properties relevant for the material's application in CLs. Besides, it also ensured a sustained release of DCF for 24 h in tests performed in hydrodynamic conditions that simulate those found in the eye, increasing significantly the amount of drug released. It reduced friction, improving the lubrication ability of the hydrogel, and presented antibacterial properties against S. aureus, P. aeruginosa and B. Cereus. The coated samples did not reveal any signs of cytotoxicity or potential eye irritation. Overall, the coating of the hydrogel may be useful to produce daily CLs able to alleviate dry eye symptoms and the discomfort of CLs wearers.

摘要

当佩戴在眼睛中时,隐形眼镜(CLs)会扰乱泪液并影响眼睛的自然摩擦学行为。眼组织之间接触力学的破坏会增加摩擦剪切应力和眼干,导致不适。最终,持续佩戴隐形眼镜会引发炎症,这对干眼症患者尤为关键。在这项工作中,采用了双重策略来获得用于干眼症的治疗性日抛型隐形眼镜:以甲基丙烯酸羟乙酯(HEMA)为基础的水凝胶涂覆有两种天然多糖,壳聚糖(CHI)和透明质酸(HA),并随后负载一种抗炎药物(双氯芬酸,DCF)。材料灭菌通过高静水压(HHP)结合适度温度进行。使用纳米摩擦计在不同泪液生物分子(胆固醇、溶菌酶和白蛋白)存在的情况下测定摩擦系数(μ)。在静态和流体动力学条件下进行药物释放实验。对材料进行了广泛的表征,包括表面形态/形貌、光学性质、含水量和溶胀行为、润湿性、离子和氧气渗透性以及机械性能。结果发现,该涂层不会损害与材料在隐形眼镜中的应用相关的物理化学性质。此外,在模拟眼睛中发现的流体动力学条件下进行的测试中,它还确保了DCF持续释放24小时,显著增加了药物释放量。它降低了摩擦力,提高了水凝胶的润滑能力,并对金黄色葡萄球菌、铜绿假单胞菌和蜡样芽孢杆菌具有抗菌性能。涂覆后的样品未显示出任何细胞毒性或潜在的眼部刺激迹象。总体而言,水凝胶涂层可能有助于生产能够缓解干眼症症状和隐形眼镜佩戴者不适的日抛型隐形眼镜。

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