Data-based modeling of drug penetration relates human skin barrier function to the interplay of diffusivity and free-energy profiles

• DOI: 10.1073/pnas.1620636114
• Publication Date: 2017-03-21T00:55:39Z
• Authors: Robert Schulz; Kenji Yamamoto; André Klossek; Roman Flesch; Stefan Hönzke; Fiorenza Rancan; Annika Vogt; Ulrike Blume-Peytavi; Sarah Hedtrich; Monika Schäfer-Ko...; Eckart Rühl; Roland R. Netz
• Keywords: 0301 basic medicine; 2. Zero hunger; Microscopy; diffusion, data-based modeling, biological barriers, skin, Smoluchowski equation; skin; 0303 health sciences; biological barriers; Skin Absorption; X-Rays; diffusion; 500 Naturwissenschaften und Mathematik::530 Physik::530 Physik; Administration, Cutaneous; 530; Dexamethasone; 3. Good health; Diffusion; data-based modeling; 03 medical and health sciences; Models, Chemical; Smoluchowski equation; 13. Climate action; 615; Humans; Epidermis; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik

Significance Human skin consists of distinct layers and is designed to prevent water loss and to keep harmful materials out, which makes transcutaneous drug delivery challenging. A model for drug diffusion within skin is introduced that as the only input requires experimental concentration profiles measured at three distinct penetration times. For the specific example of the antiinflammatory drug dexamethasone, the modeling shows that both free-energy and diffusivity profiles are highly inhomogeneous, which reveals the basic mechanism of epidermal barrier function: slow diffusion in the outer stratum corneum hinders fast penetration into the skin, whereas a pronounced free-energy step from the epidermis to the dermis underneath reduces long-time permeation. Targeted drug delivery strategies through skin must reflect these properties.