用于评估药物在角膜渗透的体外和离体模型,Molecular Pharmaceutics

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用于评估药物在角膜渗透的体外和离体模型
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2023-06-14 , DOI: 10.1021/acs.molpharmaceut.3c00195
Inès De Hoon _{1,

2} , Rabah Boukherroub ₁ , Stefaan C De Smedt ₂ , Sabine Szunerits ₁ , Félix Sauvage ₂

Affiliation

由于其独特而复杂的解剖学和生理学，药物在角膜上的渗透仍然是一个重大挑战。静态屏障（例如角膜的不同层）以及动态方面（例如泪膜的不断更新和粘蛋白层与外排泵的存在）都对有效的眼科药物输送提出了独特的挑战。为了克服当前眼科药物的一些局限性，脂质体、纳米乳剂和纳米颗粒等新型药物制剂的鉴定和测试开始被考虑和广泛探索。在角膜药物开发的早期阶段，体外和离体可靠需要有符合 3R（替换、减少和细化）原则的替代方法，这些方法也是体内研究更快、更道德的替代方法。眼科领域仍然仅限于少数眼科药物渗透的预测模型。在经角膜渗透研究中，越来越多地使用体外细胞培养模型。使用猪眼等切除的动物组织的离体模型是研究角膜渗透的首选模型，多年来已经报道了有希望的进展。使用此类模型时必须详细考虑种间特征。这篇综述更新了当前关于体外和离体角膜通透性模型并评估其优点和局限性。

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In Vitro and Ex Vivo Models for Assessing Drug Permeation across the Cornea

Drug permeation across the cornea remains a major challenge due to its unique and complex anatomy and physiology. Static barriers such as the different layers of the cornea, as well as dynamic aspects such as the constant renewal of the tear film and the presence of the mucin layer together with efflux pumps, all present unique challenges for effective ophthalmic drug delivery. To overcome some of the current ophthalmic drug limitations, the identification and testing of novel drug formulations such as liposomes, nanoemulsions, and nanoparticles began to be considered and widely explored. In the early stages of corneal drug development reliable in vitro and ex vivo alternatives, are required, to be in line with the principles of the 3Rs (Replacement, Reduction, and Refinement), with such methods being in addition faster and more ethical alternatives to in vivo studies. The ocular field remains limited to a handful of predictive models for ophthalmic drug permeation. In vitro cell culture models are increasingly used when it comes to transcorneal permeation studies. Ex vivo models using excised animal tissue such as porcine eyes are the model of choice to study corneal permeation and promising advancements have been reported over the years. Interspecies characteristics must be considered in detail when using such models. This review updates the current knowledge about in vitro and ex vivo corneal permeability models and evaluates their advantages and limitations.

更新日期：2023-06-14

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