Department of Chemical Engineering, McMaster University, Hamilton, ON, Canada.
J Biomater Sci Polym Ed. 2022 Oct;33(15):1924-1938. doi: 10.1080/09205063.2022.2088531. Epub 2022 Jun 20.
The use of hydrogel-based contact lens materials holds promise for ophthalmic drug delivery by increasing drug residence time, improving drug bioavailability, reducing administration frequency, and enhancing special site targeting. Issues such as ease of manufacturing, lens comfort and appropriate release kinetics must be considered. Furthermore, the high water content of hydrogel materials can result in rapid and poorly controlled release kinetics. Herein, we modified common hydrogels used in contact lens manufacturing with phenylboronic acid (PBA). PBA addresses these material design issues since boronate esters are easily formed when boron acid and diols interact, opening up a pathway for simple modification of the model lens materials with saccharide based wetting agents. The wetting agents have the potential to improve lens comfort. Furthermore, the hydrophobicity of PBA and the presence of diols can be useful to help control drug release kinetics. In this work, polymerizable 3-(acrylamido)phenylboronic acid (APBA) was synthesized and incorporated into various hydrogels used in contact lens applications, including poly(2-hydroxyethylmethacrylate) (PHEMA), polyvinylpyrrolidone (PVP) and poly(,dimethyl acrylamide) (PDMA) using UV induced free radical polymerization. The APBA structure and its incorporation into the hydrogel materials were confirmed by NMR and FTIR. The materials were shown to interact with and bind wetting agents such as hyaluronan (HA) and hydroxypropyl guar (HPG) by simple soaking in an aqueous solution. The equilibrium water content of the modified materials was characterized, demonstrating that most materials are still in the appropriate range after the introduction of the hydrophobic PBA. The release of three model ophthalmic drugs with varying hydrophilicity, atropine, atropine sulfate and dexamethasone, was examined. The presence of PBA in the materials was found to promote sustained drug release due to its hydrophobic nature. The results suggest that the modification of the materials with PBA was able to not only provide a mucoadhesive property that enhanced wetting agent interactions with the materials, but had the potential to alter drug release. Thus, the modification of contact lens materials with mucoadhesive functionality may be useful in the design of hydrogel contact lenses for ophthalmic drug release and wetting agent binding.
水凝胶基隐形眼镜材料的应用有望通过增加药物滞留时间、提高药物生物利用度、减少给药频率和增强特殊部位靶向作用来实现眼科药物输送。必须考虑易于制造、镜片舒适度和适当的释放动力学等问题。此外，水凝胶材料的高含水量会导致快速且控制不佳的释放动力学。在此，我们用苯硼酸（PBA）修饰了隐形眼镜制造中常用的普通水凝胶。硼酸酯很容易在硼酸和二醇相互作用时形成，这使得用糖基润湿剂简单修饰模型镜片材料成为可能，从而解决了这些材料设计问题。润湿剂有可能提高镜片舒适度。此外，PBA 的疏水性和二醇的存在有助于控制药物释放动力学。在这项工作中，合成了可聚合的 3-（丙烯酰胺基）苯硼酸（APBA），并通过 UV 诱导的自由基聚合将其掺入各种隐形眼镜应用中使用的水凝胶材料中，包括聚（2-羟乙基甲基丙烯酸酯）（PHEMA）、聚乙烯吡咯烷酮（PVP）和聚（二甲基丙烯酰胺）（PDMA）。通过 NMR 和 FTIR 证实了 APBA 结构及其在水凝胶材料中的掺入。通过简单地将材料浸泡在水溶液中，证明材料与润湿剂（如透明质酸（HA）和羟丙基瓜尔胶（HPG））相互作用并结合。改性材料的平衡水含量进行了表征，结果表明，在引入疏水性 PBA 后，大多数材料仍处于合适的范围内。考察了三种具有不同亲水性的模型眼科药物（阿托品、硫酸阿托品和地塞米松）的释放情况。结果表明，由于 PBA 的疏水性，材料中存在 PBA 会促进药物持续释放。结果表明，用 PBA 修饰材料不仅能够提供增强润湿剂与材料相互作用的粘弹性，而且有可能改变药物释放。因此，用粘弹性修饰隐形眼镜材料可能有助于设计用于眼科药物释放和润湿剂结合的水凝胶隐形眼镜。
