MORPHOLOGIC BASIS FOR A PORE-PATHWAY IN MAMMALIAN STRATUM-CORNEUM

Although prior morphologic studies have shown that both polar and nonp olar materials permeate across the stratum corneum (SC) via a paracell ular route, the actual pathway through these heterogeneous domains is unknown. We applied hydrophilic and hydrophobic tracers in vivo to mur ine skin under basal conditions and/or after permeation enhancement wi th occlusion, vehicle enhancers, a lipid synthesis inhibitor, sonophor esis, and iontophoresis. Ruthenium tetroxide, ruthenium red plus osmiu m tetroxide, in situ precipitation with osmium vapor, and microwave po stfixation methods were used to visualize penetration pathways. Tracer s invariably localized to discrete lacunar domains, embedded within th e extracellular lamellar membrane system, regardless of their polarity or the enhancement method. Moreover, while the lacunar domains remain ed discontinuous under basal conditions, they appeared to gain structu ral continuity with permeation enhancement. These results indicate tha t extracellular lacunar domains comprise a pore pathway for penetratio n of polar and nonpolar molecules across the SC.