In vitro models for evaluating safety and efficacy of novel technologies for skin drug delivery.

For preclinical testing of novel therapeutics, predictive in vitro models of the human skin are required to assess efficacy, absorption and safety. Simple as well as more sophisticated three-dimensional organotypic models of the human skin emerged as versatile and powerful tools simulating healthy as well as diseased skin states. Besides addressing the demands of research and industry, such models serve as valid alternative to animal testing. Recently, the acceptance of several models by regulatory authorities corroborates their role as important building block for preclinical development. However, valid assessment of readout parameters derived from these models requires suitable analytical techniques. Standard analytical methods are mostly destructive and limited regarding in-depth investigation on molecular level. The combination of adequate in vitro models with modern non-invasive analytical modalities bears a great potential to address important skin drug delivery related questions. Topics of interest are for instance the assessment of repeated dosing effects and xenobiotic biotransformation, which cannot be analyzed by destructive techniques. This review provides a comprehensive overview of current in vitro skin models differing in functional complexity and mimicking healthy as well as diseased skin states. Further, benefits and limitations regarding analytical evaluation of efficacy, absorption and safety of novel drug carrier systems applied to such models are discussed along with a prospective view of anticipated future directions. In addition, emerging non-invasive imaging modalities are introduced and their significance and potential to advance current knowledge in the field of skin drug delivery is explored.