TY - JOUR A1 - Schulz, Robert A1 - Yamamoto, Kenji A1 - Klossek, André A1 - Rancan, Fiorenza A1 - Vogt, Annika A1 - Schütte, Christof A1 - Rühl, Eckart A1 - Netz, Roland R. T1 - Modeling of Drug Diffusion Based on Concentration Profiles in Healthy and Damaged Human Skin T2 - Biophysical Journal N2 - Based on experimental drug concentration profiles in healthy as well as tape-stripped ex vivo human skin, we model the penetration of the antiinflammatory drug dexamethasone into the skin layers by the one-dimensional generalized diffusion equation. We estimate the position-dependent free-energy and diffusivity profiles by solving the conjugated minimization problem, in which the only inputs are concentration profiles of dexamethasone in skin at three consecutive penetration times. The resulting free-energy profiles for damaged and healthy skin show only minor differences. In contrast, the drug diffusivity in the first 10 μm of the upper skin layer of damaged skin is 200-fold increased compared to healthy skin, which reflects the corrupted barrier function of tape-stripped skin. For the case of healthy skin, we examine the robustness of our method by analyzing the behavior of the extracted skin parameters when the number of input and output parameters are reduced. We also discuss techniques for the regularization of our parameter extraction method. Y1 - 2019 UR - https://opus4.kobv.de/opus4-zib/frontdoor/index/index/docId/7583 VL - 117 IS - 5 SP - 998 EP - 1008 ER -