MICA: Antimicrobial bandage contact lenses

角膜是眼睛前方的透明窗口。在角膜手术或各种治疗后，经常使用绷带隐形眼镜来保护角膜并增加患者的舒适度。为了减少感染的风险，通常还会使用抗生素。在这个项目中，我们将创造一种新型的隐形眼镜，将这两种工艺结合起来。我们开发了一种新型水凝胶，它具有高含水量，优异的透明度和与现有水凝胶隐形眼镜相似的机械性能。这种新型水凝胶的特殊优势在于它是天然抗菌的，不像任何现有的材料。水凝胶是在室温下在水中合成的，而现有的隐形眼镜材料在合成过程中需要使用有毒溶剂，然后需要大量的洗涤过程来去除它们。我们已经证明，这种新型水凝胶可以使用现有的成型工艺铸造到隐形眼镜中。我们假设在手术后或角膜交联等干预后使用抗菌绷带隐形眼镜会增加舒适度并减少感染。在这项研究中，我们将优化新型水凝胶的组成，充分表征其抗菌和生物相容性，并在人体健康志愿者试验中评估其安全性。这项研究的第二部分将开发一种治疗性隐形眼镜。角膜感染是影响角膜最常见的疾病之一，占全球失明病例的5%。为了视力而佩戴隐形眼镜与角膜感染增加6倍有关。角膜感染的治疗依赖于频繁使用抗生素滴剂；在最初的48小时内，每5-15分钟常规一次，然后在1-2周内每2-6小时。隐形眼镜以持续和可控的方式提供治疗剂量的抗菌药物将提供更有效的治疗策略并增强传统治疗。角膜感染可由细菌和真菌引起，每种细菌和真菌都需要不同的抗感染药物治疗。我们已经证明，我们的新型水凝胶可以装载抗生素和抗真菌药物，这些药物在治疗水平上释放，可以杀死培养中的细菌和真菌。在这项研究中，我们将优化水凝胶的组成，以开发含有特定抗生素和抗真菌药物的绷带隐形眼镜，用于治疗角膜感染。我们将在实验室实验中充分表征它们的抗感染和细胞相容性，使用细菌、真菌和角膜细胞进行培养，并在眼睛前部的器官培养模型中进行实验。此外，我们将使用分析抗菌素耐药性遗传基础的方法，调查细菌和真菌物种是否能够在添加和不添加药物的情况下对水凝胶产生耐药性。在这个项目中，我们将与两家公司合作；一个在水凝胶合成方面有经验，另一个在隐形眼镜制造方面有丰富的经验。在项目结束时，我们打算制造出1)一种安全的绷带隐形眼镜，它有可能增加角膜手术后患者的舒适度，并降低感染的风险；2)一种治疗性绷带隐形眼镜，它能提供临床相关的抗生素和抗真菌药物，达到治疗水平，在实验室中已被证明能有效杀死临床相关的细菌和真菌。

The cornea is the clear window at the front of the eye. Following surgery or various treatments to the cornea a bandage contact lens will frequently be used to protect the cornea and increase comfort for the patient. To reduce the risk of infection antibiotics will also normally be administered. In this project we will create a new type of contact lens that will combine both these processes. We have developed a novel hydrogel with a high water content, excellent transparency and mechanical properties similar to those of existing hydrogel contact lenses. The specific advantage of this new hydrogel is that it is naturally antimicrobial, unlike any of the existing materials. The hydrogel is synthesised in water at room temperature, whereas existing contact lens materials require the use the toxic solvents during synthesis and then need extensive washing procedures to remove them. We have shown that the novel hydrogel can be cast into a contact lens using existing moulding processes. We hypothesise that use of an antimicrobial bandage contact lens post-surgery or after an intervention such as corneal crosslinking, would increase comfort and reduce infection. In this study we will optimise the composition of the new hydrogel, fully characterise its antimicrobial and biocompatibility properties and evaluate its safety in a human healthy volunteer trial. A second strand of this study will develop a therapeutic contact lens. Corneal infection is one of the commonest conditions affecting the cornea, accounting for 5% of cases of blindness worldwide. Contact lenses worn for vision are associated with a six fold increase in corneal infection. Treatment of corneal infection relies on frequent application of antibiotic drops; routinely every 5-15 minutes for the first 48 hours, then 2-6 hourly over 1-2 weeks. Contact lenses delivering therapeutic doses of antimicrobial drugs in a sustained and controlled manner would provide a more effective treatment strategy and augment conventional treatments. Corneal infection can be caused by both bacteria and fungi with each particular species requiring a different anti-infection drug treatment. We have demonstrated that our novel hydrogel can be loaded with antibiotic and antifungal drugs that are released at therapeutic levels that can kill bacteria and fungi in culture. In this study we will optimise the composition of the hydrogel to develop bandage contact lenses containing specific antibiotic and antifungal drugs that are used to treat corneal infections. We will fully characterise their anti-infection and cell compatibility properties in laboratory experiments using bacteria, fungi and corneal cells in culture and in an organ culture model of the front of the eye. Furthermore we will investigate if the bacteria and fungi species are able to develop resistance to the hydrogel with and without the added drugs using methods that analyse the genetic basis of antimicrobial resistance.During this project we will collaborate with two companies; one with experience in the hydrogel synthesis and the other with extensive experience of contact lens manufacture. At the end of the project we intend to have 1) a bandage contact lens that is safe and has the potential to increase comfort for patients post corneal surgery and to reduce the risk of infection and 2) a therapeutic bandage contact lens that delivers clinically relevant antibiotics and antifungal drugs at therapeutic levels that have been shown to be effective at killing clinically relevant bacteria and fungi in the laboratory.