STRATUM-CORNEUM, CORNEODESMOSOMES AND EX-VIVO PERCUTANEOUS PENETRATION

The stratum corneum is composed of cornified keratinocytes, joined tog ether with corneodesmosomes and embedded in the relatively hydrophobic intercellular substance. Formation of this horny layer and its consta nt desquamation are fundamental processes leading to the establishment of an efficient epidermal barrier. We examined structural changes occ urring in the stratum corneum ex vivo, in order to better understand t he mechanisms regulating corneocyte desquamation at the epidermal surf ace and influencing percutaneous penetration of exogenous substances. Morphologic modifications were induced by occlusion, increasing the ti ssue hydration, or by application of propylene glycol, a hydrophilic s olvent of small molecular size. Distribution of the major epidermal an tigens, markers of terminal differentiation, was studied immunohistoch emically and showed no modification related to the tissue alteration. Skin samples were fixed in paraformaldehyde and either postfixed in Os O4 and embedded in Epon or postfixed in RuO4 and embedded in epoxy and acrylic resins. Structural composition and spatial organization of th e elements present in the intercorneocyte spaces were evaluated ultras tructurally, with special attention paid to the fate of corneodesmosom es. Our results suggest that the spontaneous organization of lipids ex creted into the intercellular spaces and constitution of the lamellar multilayers in the lower stratum corneum are at the origin of partitio n of the intercellular compartment to the hydrophobic and hydrophilic domains. The latter, compatible with the proteinic contents, seem to b e displaced by the hydrophobic components undergoing reorganization, t owards the invariable hydrophilic foci represented by corneodesmosomes . This mechanism may be involved in the delivery of proteolytic enzyme s, thus contributing to the progressive degradation of corneodesmosoma l proteins. (C) 1998 Wiley-Liss, Inc.