Development of a Convenient ex vivo Model for the Study of the Transcorneal Permeation of Drugs: Histological and Permeability Evaluation
Development of a Convenient ex vivo Model for the Study of the Transcorneal Permeation of Drugs: Histological and Permeability Evaluation
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DOI：
10.1002/jps.24231
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发表时间：
2015-01-01
影响因子：
3.8
通讯作者：
Nicoli, Sara
中科院分区：
文献类型：
--
作者：
Pescina, Silvia;Govoni, Paolo;Nicoli, Sara
本文以猪组织为研究对象，对药物经角膜渗透的体外模型进行了评价。该装置的特点是易于实现，没有O-2和CO2鼓泡，成本低；此外，猪组织的大量可获得性允许高产量。组织学图像显示猪和人的角膜具有可比性，证实了分离程序的有效性。还建立了一种基于热方法的新的去上皮化程序来模拟病理条件下的角膜渗透性。该程序不影响底层的完整性，并允许表征上皮和间质的屏障属性。测定了荧光素、阿替洛尔、普奈洛尔、双氯芬酸、更昔洛韦和利多卡因等6种不同理化性质的化合物。该模型强调了上皮对亲水性化合物扩散所起的屏障作用，以及对更亲油的分子的渗透选择性。特别是，带正电的化合物比带负电的化合物显示出显著更高的角膜渗透率。结果与文献数据的可比性支持了模型的优良性和稳健性，特别是考虑到荧光素的行为，这通常被认为是组织完整性的标志。(C)2014 Wiley期刊，Inc.和美国药剂师协会药学杂志104：63-71,2015
In this paper, an ex vivo model for the study of the transcorneal permeation of drugs, based on porcine tissues, was evaluated. The setup is characterized by ease of realization, absence of O-2 and CO2 bubbling and low cost; additionally, the large availability of porcine tissue permits a high throughput. Histological images showed the comparability between porcine and human corneas and confirmed the effectiveness of the isolation procedure. A new de-epithelization procedure based on a thermal approach was also set up to simulate cornea permeability in pathological conditions. The procedure did not affect the integrity of the underlying layers and allowed the characterization of the barrier properties of epithelium and stroma. Six compounds with different physicochemical properties were tested: fluorescein, atenolol, propranolol, diclofenac, ganciclovir and lidocaine. The model highlighted the barrier function played by epithelium toward the diffusion of hydrophilic compounds and the permselectivity with regard to more lipophilic molecules. In particular, positively charged compounds showed a significantly higher transcorneal permeability than negatively charged compounds. The comparability of results with literature data supports the goodness and the robustness of the model, especially taking into account the behavior of fluorescein, which is generally considered a marker of tissue integrity. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:63-71, 2015