Hydration disrupts human stratum corneum ultrastructure.

Using transmission and cryo-scanning electron microscopy, we confirm that extended water exposure leads to extensive disruption of stratum corneum intercellular lipid lamellae. We define the in vivo swelling behavior of the stratum corneum: exposure to water for 4 or 24 h results in a 3- or 4-fold expansion of the stratum corneum thickness, respectively. Corneocytes swell uniformly with the exception of the outermost and inner two to four corneocyte layers, which swell less. We show that hydration induces large pools of water in the intercellular space, pools that can exceed the size of water-swollen corneocytes. By 4 h of water exposure there are numerous small and large intercellular pools of water ("cisternae") present throughout the stratum corneum, and at 24 h these cisternae substantially increase in size. Within cisternae the lipid structure is disrupted by lamellar delamination ("roll-up"). Cisternae appear to be disk-shaped structures that do not obviously communicate. Cisternae appear to contain considerable lipidic and other material and to contain a substantial fluid volume that can rival the volume of the dry stratum corneum. Similar results are obtained following urine exposure. With urine exposure, cisternae communicate with salts in the external solution. This study illustrates the disruptive effect of overhydration on the stratum corneum intercellular space, identifies large and numerous unanticipated intercellular cisternal structures, defines the magnitude of stratum corneum swelling, and identifies stratum corneum cell layers that swell less. The study suggests the stratum corneum is a more chaotic structure than previously envisioned, and provides a framework for better understanding desquamation, irritancy, and percutaneous transport.

Hydration vs. skin permeability to nicotinates in man.

BACKGROUND/AIMS: Prolonged skin occlusion increases stratum corneum water content and often increases skin permeability and irritant dermatitis. As skin wetness from wearing diapers is considered an important factor favouring the onset of diaper dermatitis, optimal diapering might decrease skin hyperhydration and dermatitis. Our aim is to define the quantitative relationship between nicotinate ester (a model penetrant) skin permeability and hydration, as measured by water evaporation rate (WER), decay curves (at individual time points) and WER-area under the curve (WER-AUC); and also to determine the level of skin hydration and skin permeability to nicotinates following a diapering simulation. METHODS/RESULTS: Nine healthy Caucasian adult women were enrolled after a prescreening procedure (time to peak redness response to nicotinate); each received three wet occlusive patches for different exposure times (10 min, 30 min, and 3h) and two wet model diapers (3 and 8 h). Prior to patching or diapering of forearms, basal values of WER, skin blood flow volume (BFV), capacitance (Cap) and redness (a*) were measured on premarked sites (a, b, c and d). Immediately, following occlusive patch or diaper removal, 20 microL of each nicotinate (methyl and hexyl nicotinate) was applied to its respective site (a or b). The WER and Cap readings were recorded at designated sites (c and d) with the following intervals after nicotinate applications: 0, 5,10,15 and 20 min. The a* and BFV measurements were made on each nicotinate challenged site (a and b) with the following intervals after nicotinate applications: 5, 10, 15, 20, 30, 40, and 60 min. RESULTS: WER-AUC and thus, skin hyperhydration, increased with occlusive patch and diaper exposure time, but there was no statistical difference between 3 and 8h diaper sites. All patched sites had significantly (P<0.05) increased hydration in comparison to control sites (undiapered or unpatched skin). Cap increased with occlusion time with patches, but not with diapers. The degree and time-course of redness from nicotinates did not vary with extent of skin hydration, but was significantly increased compared to non-hydrated skin. BFV-AUC did not show a significant increase between diapers at 3 and 8h sites; the BFV-AUC values varied on the patched sites, but some were significantly (P<0.05) higher than control site. CONCLUSION: Wet patches and diapers increased skin hyperhydration proportional to exposure time. Permeation of nicotinates was increased for hydrated skin vs. control, even after only 10 min of patch exposure. For these model permeants, we found no evidence of increased permeation rates with increased hyperhydration, once a relatively low threshold of hyperhydration was achieved (e.g. that reached after a 10 min wet patch). The data showed no meaningful differences in permeation following either diapering simulation and also suggested that the WER-AUC method was superior to capacitance for measuring the absolute extent of hyperhydration. We believe this is a suitable model for evaluating the quality of diaper product performance, as well as in pharmacologic assays of occlusive therapy.