Effect of dipolar aprotic permeability enhancers on the basal stratum corneum

The effect of dimethyl sulfoxide, dimethyl formamide, and dimethyl acetamide on the basal stratum corneum of excised nude mouse skin was investigated. All of these dipolar aprotic solvents caused a swelling of the basal stratum corneum cells and a disruption of the normal keratin pattern. This behavior suggests that dipolar aprotic solvents might alter the barrier properties of the basal stratum corneum cells. To test this hypothesis, the distribution of topically applied, electron-dense divalent metal ions (Hg2+ and Ni2+) was studied in excised nude mouse skin which had been perturbed by the application of dipolar aprotic solvents, and in controls which had not been so treated. In control skin membranes, Hg2+ and Ni2+ were located almost exclusively in the intercellular space of the stratum corneum. However, with the application of a dipolar aprotic solvent, Hg2+ and Ni2+ were found in the intercellular spaces and inside the basal stratum corneum cells, where they appeared to be primarily associated with the cytoplasmic filaments. Sulfide precipitation allowed for the localization of Hg2+ and Ni2+, and subsequent chemical identification by energy-dispersive X-ray microanalysis. The spatial resolution of X-ray microanalysis studies was approximately 0.5-0.75 micron. The spatial alteration in mercury and nickel precipitate distribution, which occurs when the skin is pretreated with a dipolar aprotic solvent, is consistent with the hypothesis that the pathway of Hg2+ and Ni2+ diffusion through the basal stratum corneum has also been modified.