Transcellular route of diffusion through stratum corneum: Results from finite element models

Dynamics of diffusion with reversible binding in microscopically heterogeneous membranes: General theory and applications to dermal penetration

“…(51)). Barbero and Frasch (2006) have demonstrated very convincingly that the lag times for theophylline and a host of other hydrophilic compounds imply a picture in which the transcellular diffusion pathway is the dominant contributor to solute flux. (Lag times based on an impermeable corneocyte model (i.e.,…”

“…allowing partitioning into and diffusion through only the lipid phase) are too short to match experimental data (Barbero and Frasch, 2006); this conclusion may in fact apply across the board to most permeants, including lipophilic ones (Wang et al, 2007).) Therefore it is very appropriate to employ the well known onedimensional resistances-in-series formula for D used in the main text (Eq.…”

“…The apparent lag time for water diffusion through the SC is 20-30 min (Scheuplein, 1965;Barbero and Frasch, 2006;Wang et al, 2007), and corresponding values for other chemical species are usually larger, often considerably (e.g. 8.3 h for nicotinamide, 9.2 h for testosterone (Kasting et al, 2005;Barbero and Frasch, 2006;Wang et al, 2007)). Steady state is usually deemed to have been reached after 2-3 lag times.…”

Safety of Nanoparticles

“…Polar substances move para-and trans-cellularly in association with proteins through tightly linked corneocytes or para-cellularly between corneocytes through polar channels formed in lipid lamellae (Dayan 2005). Both mechanisms are important however, finite element modeling and literature data suggest that permeation primarily occurs transcellularly through corneocytes, causing very high lag times for polar substances (Barbero and Frasch 2006). Skin tends to be far more permeable to hydrophobic substances, whose main route of entry is intercellularly between corneocytes through the lipid lamellae ( Fig.…”

Current Understanding of Skin Barrier Morphology

“…With the discovery in the 1960s-1970s that the extracellular space was filled with fat material [6,7,8], it was natural to assume that the major, but not exclusive, penetration pathway for lipid-soluble molecules was extracellular and for water-soluble molecules transcellular [19], underlining the importance for skin permeability of horny layer geometry [20], partitioning and reversible binding to the tissue. Although hotly debated, this view still largely holds today [21,22,23,24,25,26,27,28]. Other basic concepts already established in the 1970s were that macroscopically the horny layer is uniformly impermeable and behaves like a passive diffusion barrier.…”