Three-dimensional skin models as tools for transdermal drug delivery: challenges and limitations

Introduction: 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. Areas covered: 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. Expert opinion: 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.