Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma, Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Biomater Sci. 2020 Feb 21;8(4):1171-1180. doi: 10.1039/c9bm01582e. Epub 2020 Jan 29.
Contact lenses (CLs) are being pointed out as feasible platforms for controlled delivery of ophthalmic drugs. Bioinspired strategies may endow CLs with affinity for a given drug by mimicking its physiological receptor using adequate functional monomers and tuning their conformation in the space through the molecular imprinting technology. However, there are some active substances, such as efficient antioxidant agents, that cannot be used as templates because they degrade during polymerization or even hinder the polymerization itself. Therefore, the development of CLs able to sustain the release of antioxidants for the prevention and/or treatment of several age-related and light-induced eye diseases has not been explored yet. Searching for an alternative bioinspired strategy, the present work relies on the fact that some drugs owe their therapeutic action to their ability to interact with nucleotides that build up DNA and RNA. Thus, the aim of this work was to design hydrogels functionalized with the nitrogenous base cytosine for the controlled uptake and release of transferulic acid (TA) having a complementary chemical structure in terms of hydrogen bonding and π-π stacking ability. Hydrogels were prepared from mixtures of 2-hydroxyethyl methacrylate (HEMA), glycidyl methacrylate (GMA) and ethyleneglycolphenylether methacrylate (EGPEM). GMA was used as a bridge to immobilize cytosine after hydrogel synthesis, while EGPEM was added to reinforce hydrophobic interactions with TA. The hydrogels were characterized in terms of suitability to be used as CLs (swelling, light transmission, mechanical properties, biocompatibility) and capability to host TA and sustain its release in lachrymal fluid while maintaining the antioxidant activity. Relevantly, the bioinspired CLs favored TA accumulation in cornea and sclera tissues.
隐形眼镜 (CL) 被认为是眼科药物控释的可行平台。仿生策略可以通过使用适当的功能单体模拟给定药物的生理受体，并通过分子印迹技术在空间中调整其构象，从而使 CL 对特定药物具有亲和力。然而，有些活性物质，如高效抗氧化剂，不能用作模板，因为它们在聚合过程中会降解，甚至阻碍聚合本身。因此，尚未探索开发能够持续释放抗氧化剂的 CL 以预防和/或治疗几种与年龄相关和光诱导的眼部疾病。为了寻找替代的仿生策略，本工作依赖于这样一个事实，即一些药物的治疗作用归因于它们与构成 DNA 和 RNA 的核苷酸相互作用的能力。因此，本工作的目的是设计用含氮碱基胞嘧啶功能化的水凝胶，用于控制摄取和释放具有互补化学结构（就氢键和 π-π 堆积能力而言）的转移芦丁酸 (TA)。水凝胶由 2-羟乙基甲基丙烯酸酯 (HEMA)、甲基丙烯酸缩水甘油酯 (GMA) 和乙氧基苯乙基甲基丙烯酸酯 (EGPEM) 的混合物制备而成。GMA 用于在水凝胶合成后固定胞嘧啶，而 EGPEM 则用于增强与 TA 的疏水相互作用。水凝胶在适合用作 CLs 的方面进行了表征（溶胀、透光率、机械性能、生物相容性），并具有容纳 TA 和在泪液中持续释放 TA 同时保持抗氧化活性的能力。相关地，仿生 CLs 有利于 TA 在角膜和巩膜组织中的积累。
