[Tridimensional skin models recording percutaneous absorption] [Article in German]

Abstract

Today there is a lack of generally accepted alternatives to animal experiments for the evaluation of percutaneous absorption or skin penetration. To evaluate the potential of commercially available reconstructed epidermis we compared the barrier function of the three dimensional human skin equivalents Episkin™, EpiDerm™, and Skinethic™ to those of excised human skin. Moreover the batch-to-batch variation of skin equivalents was determined. Methods for evaluation included the determination of transepidermal water loss (TEWL) and of the prednisolone (PD) penetration. Whereas TEWL values of Skinethic™ and EpiDerm™ were very close (15 g·m-2·h-1), PD-penetration showed a clearly superior barrier function with the Skinethic™ model. Drug penetration was only 50% of the EpiDerm™ model and PD concentrations in the acceptor medium amounted to 150 ng/ml as compared to 300 ng/ml. The highest values were obtained with the Episkin™ model (20 g·m-2·h-1, 500 ng/ml). Therefore this model has the poorest barrier function. The TEWL value for human skin was 9 g·m-2·h-1 and PD concentrations in the acceptor medium were below the limit of detection (10.1 ng/ml).
Because of the superior barrier function of the Skinethic™ the following evaluation was only performed using this model. Batch-to-batch variation was less than with human skin (interindividual variation of 2 h TEWL 12% and > 19%). Despite of the slightly less well-developed barrier, this skin model clearly appears superior with respect to the reproducibility of data. Therefore future investigations on the potential of human skin equivalents for the determination of percutaneous absorption appear very promising.