Hydration vs. skin permeability to nicotinates in man.

Abstract

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. 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. 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. 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.