Ghent University Hospital, Department of Dermatology, Belgium.
Expert Opin Drug Deliv. 2011 Jun;8(6):705-20. doi: 10.1517/17425247.2011.568937. Epub 2011 Mar 30.
Transdermal drug delivery has several known advantages over the oral route and hypodermic injections. The number of drugs that can be taken up transdermally is, however, limited owing to the innate barrier function of the skin. New transdermal drug candidates need to be tested extensively before being used on humans. In this regard, in vitro permeation methods are highly important to predict in vivo permeation of drugs.
This review illustrates how different types of reconstructed skin models are being used as alternatives to human and pig skin for in vitro permeation testing of drugs. Insights into how various factors (including the physicochemical nature of molecules and formulations) or skin properties might affect the permeability of drugs in reconstructed skin models are provided. Also, opportunities and pitfalls of reconstructed skin models are highlighted.
Many studies have revealed that the permeability of reconstructed skin models is much higher compared with human excised skin. This is in accordance with the incomplete barrier found in these models. Nevertheless, the reconstructed skin models available today are useful tools for estimating the rank order of percutaneous absorption of a series of compounds with different physicochemical properties. A major challenge in the further development of reconstructed skin models for drug delivery studies is to obtain a barrier function similar to in vivo skin. Whether this goal will be achieved in the near future is uncertain and will be, in the authors' opinion, a very difficult task.
与口服途径和皮下注射相比,经皮给药具有许多已知的优势。然而,由于皮肤固有的屏障功能,能够经皮吸收的药物数量是有限的。在将新的经皮药物候选物用于人体之前,需要对其进行广泛的测试。在这方面,体外渗透方法对于预测药物的体内渗透非常重要。
本文说明了不同类型的重建皮肤模型如何被用作替代人体和猪皮,用于药物的体外渗透测试。本文还提供了关于各种因素(包括分子和制剂的物理化学性质)或皮肤特性如何影响药物在重建皮肤模型中的渗透性的见解。此外,还强调了重建皮肤模型的机会和陷阱。
许多研究表明,与人体离体皮肤相比,重建皮肤模型的渗透性要高得多。这与这些模型中发现的不完全屏障是一致的。然而,目前可用的重建皮肤模型是用于估计一系列具有不同物理化学性质的化合物经皮吸收顺序的有用工具。用于药物输送研究的重建皮肤模型进一步发展的主要挑战是获得类似于体内皮肤的屏障功能。在不久的将来是否能够实现这一目标尚不确定,作者认为,这将是一项非常艰巨的任务。