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Our study highlights the importance of the gastrointestinal lipolysis and the associated phenomena such as the dilution of chyme by biliary and pancreatic secretions in vivo, on the solubilisation of poorly water-soluble drugs formulated with lipid-based excipients.

Several tight junction (TJ) proteins were detected in the living layers of adult human epidermis, and TJ-like membrane ridges were observed at the top of the stratum granulosum (SG) in freeze-fracture studies. We applied standard and immunoelectron microscopy to look for TJ-derived structures in the stratum corneum (SC) of human adult epidermis and in cornified envelopes purified from the plantar SC. Besides confirming claudin-1 labelling in the proximity of SG desmosomes, we also observed immunolocalization near corneodesmosomes in the lower SC. In addition, TJ proteins were consistently detected in the purified cornified envelopes. Lateral but not horizontal walls of the corneocytes showed frequent points of molecular fusion between lipid envelopes. These structural associations were very frequently localized at the top of the lateral corneocyte membranes, thus sealing the extremities of lateral intercorneocyte spaces. We propose that TJ-like structures persist in the SC and contribute to the reinforcement of lateral contacts and to the formation of membrane interdigitations between corneocytes. Their presence could contribute to subdivision of the extracellular spaces of SC into consecutive individualized compartments. Intercellular lipids, enzymes and other (glyco)protein content could thus evolve in the keratinized epidermal layer at different paces, as preprogrammed in the underlying living cells and influenced by the environment, e.g. humidity. Such situation might explain differences in the degradation rates between the 'peripheral' and the 'non-peripheral' corneodesmosomes observed during physiological desquamation, as previously suggested by us and others.Key words: cornified envelopes -desquamation -epidermal cohesionstratum corneum -tight junctions Accepted for publication 26 April 2011Human stratum corneum (SC) is the final product of epidermal differentiation that provides barrier function to the skin. Composed of cornified epithelial cells, called corneocytes, and sealed with the lipid-rich extracellular matrix, this thin epidermal layer is relatively impermeable to water and water-soluble substances. Like the entire epidermis, SC is constantly recycled in a highly regulated and interactive process in which superficial cell losses by desquamation at the skin surface are readily compensated by the conversion of the uppermost living keratinocytes into corneocytes (1,2). Such a programmed cell death is associated with several important changes in the cell shape and structure leading to the accumulation of flattened, laterally interdigitated, cornified keratinocytes forming the lower part of the SC, the SC compactum. During cornification, phospholipids of the keratinocyte plasma membrane are replaced by a single layer of ceramides. The latter are covalently bound by transglutaminase 1 to the protein envelope that is also cross-linked at the cell periphery by the same enzyme (3,4). The proper functioning of the SC barrier depends largely on its cohesion. Therefore, it is important to note tha...