Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, R+D Pharma Group (GI-1645), Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
HGBeyond Materials Science S.L, Edificio Emprendia, Campus Vida s/n, 15782 Santiago de Compostela, Spain.
Acta Biomater. 2019 Jan 15;84:49-62. doi: 10.1016/j.actbio.2018.11.020. Epub 2018 Nov 16.
Efficient ocular drug delivery that can overcome the challenges of topical application has been largely pursued. Contact lenses (CLs) may act as light-transparent cornea/sclera bandages for prolonged drug release towards the post-lens tear fluid, if their composition and inner architecture are fitted to the features of the drug molecules. In this review, first the foundations and advantages of using CLs as ocular drug depots are revisited. Then, pros and cons of common strategies to prepare drug-loaded CLs are analyzed on the basis of recent examples, and finally the main section focuses on bioinspired strategies that can overcome some limitations of current designs. Most bioinspired strategies resemble a reverse engineering process to create artificial receptors for the drug inside the CL network by mimicking the human natural binding site of the drug. Related bioinspired strategies are being also tested for designing CLs that elute comfort ingredients mimicking the blinking-associated renewal of eye mucins. Other bioinspired approaches exploit the natural eye variables as stimuli to trigger drug release or take benefit of bio-glues to specifically bind active components to the CL surface. Overall, biomimicking approaches are being revealed as valuable tools to fit the amounts loaded and the release profiles to the therapeutic demands of each pathology. STATEMENT OF SIGNIFICANCE: Biomimetic and bioinspired strategies are remarkable tools for the optimization of drug delivery systems. Translation of the knowledge about how drugs interact with the natural pharmacological receptor and about components and dynamics of anterior eye segment may shed light on the design criteria for obtaining efficient drug-eluting CLs. Current strategies for endowing CLs with controlled drug release performance still require optimization regarding amount loaded, drug retained in the CL structure during storage, regulation of drug release once applied onto the eye, and maintenance of CL physical properties. All these limitations may be addressed through a variety of recently growing bioinspired approaches, which are expected to pave the way of medicated CLs towards the clinics.
人们一直在寻求能够克服局部应用挑战的高效眼部药物输送方法。如果隐形眼镜 (CL) 的组成和内部结构符合药物分子的特征,那么它们可以作为光透明的角膜/巩膜绷带,将药物长时间释放到隐形眼镜后的泪液中。在这篇综述中,首先回顾了将 CL 用作眼部药物储存库的基础和优势。然后,根据最近的实例分析了制备载药 CL 的常见策略的优缺点,最后主要部分重点介绍了可以克服当前设计局限性的仿生策略。大多数仿生策略通过模仿药物在 CL 网络内的人类天然结合部位,为药物创造人工受体,类似于反向工程过程。相关仿生策略也正在被测试用于设计释放模仿眨眼相关的眼部黏液更新的舒适成分的 CL。其他仿生方法利用自然眼部变量作为刺激物来触发药物释放,或者利用生物胶将活性成分特异性结合到 CL 表面。总的来说,仿生方法被证明是一种有价值的工具,可以根据每种疾病的治疗需求来调整加载量和释放曲线。
仿生和生物灵感策略是优化药物输送系统的重要工具。了解药物如何与天然药理学受体相互作用以及前眼部段的成分和动力学的知识,可以为获得高效药物洗脱 CL 的设计标准提供启示。目前使 CL 具有控制药物释放性能的策略仍然需要在以下方面进行优化:加载量、储存过程中 CL 结构中保留的药物、应用于眼睛后药物释放的调节以及 CL 物理性能的维持。所有这些限制都可以通过各种最近出现的生物灵感方法来解决,这些方法有望为载药 CL 走向临床铺平道路。