We argue that this is a result of two opposing effects – dehydration from low water activity and retention of high skin permeability properties. When glycerol or urea is subsequently added to the formulations the water activity is lowered to approx. 0.9 (Table 1). This decrease in water activity C59 purchase does not lead to a decrease in the Mz flux, which is in contrast to what is observed when the

water activity is lowered by addition of PEG in absence of glycerol or urea (Fig. 1A). By comparing flux values from either glycerol or urea formulations to flux values from PEG formulations at similar water activities in Fig. 1A it is clear that the difference in Mz flux is substantial. These results demonstrate that addition of either glycerol or urea to water-based formulations can act to retain the permeability properties associated with a fully hydrated skin membrane at dehydrating conditions. In the second case, when the polymer PEG is added to the donor formulations that also contain glycerol or urea, the water activity is further decreased to approx. 0.8 (Table 1). In this case, the corresponding flux data show that the onset of the sharp MAPK Inhibitor Library screening decrease in Mz flux is shifted towards considerably lower water activities as compared to the case of PEG in neat PBS solution

(Fig. 1B). Also, by comparing flux values at similar water activities from the different formulations it is clear that the formulations containing glycerol or urea results in increased Mz flux. The variation in skin permeability

of Mz with hydration observed in Fig. 1B should be considered in relation to previous in vitro studies on water diffusion across SC as a function of RH ( Alonso et al., 1996 and Blank et al., 1984), demonstrating an abrupt change of skin permeability to water at approx. 85–95% RH. In previous studies ( Björklund et al., 2010), we demonstrated the same ADP ribosylation factor qualitative behavior for skin permeability of Mz at varying water activity (see the relation between aw and RH in Section 2.6), although the position of the abrupt change was observed at higher values of water activity (RH) (ref. data in Fig. 1). In the present study we show that the onset of the abrupt increase can be shifted towards lower water activities (RHs) by adding glycerol or urea to the SC samples ( Fig. 1B). This implies that the presence of glycerol or urea, as well as other small polar NMF compounds, may actually determine the position in terms of water activity for which there is an abrupt change in SC permeability towards water and other compounds. This could be of significance for the interplay between, TEWL, SC hydration, and biochemical processes ( Harding et al., 2000). Glycerol and urea can act to retain as high permeability of Mz as a fully hydrated skin membrane at reduced water activities (Fig. 1A).