Short chain alkanols as transport enhancers for lipophilic and polar/ionic permeants in hairless mouse skin: Mechanism(s) of action

Abstract

The influences of short chain n-alkanols (from C1 to C5) and isopropanol on the transport of lipophilic (β-estradiol and hydrocortisone) and polar/ionic (tetraethylammonium ion) permeants across hairless mouse skin have been investigated. Permeability studies employing a two-chamber diffusion cell were carried out over wide ranges of alkanol (in saline) concentrations with an aim toward quantifying the reversible enhancement effects of the added alkanol upon the lipoidal pathway of the stratum corneum. An enhancement factor, E (for the lipoidal pathway of the stratum corneum), was calculated from permeability coefficient and solubility data, and the E values for β-estradiol and for hydrocortisone were found to be nearly always the same in all instances. A pattern of increasing E values with increasing alkanol chain length up to C5 with these two permeants was found. A nearly semi-logarithmic linear relationship was also obtained between the enhancement potency and the carbon number of the n-alkanols; there was about 4-fold increase in the enhancement potency per n-alkanol methylene group. Pretreatment studies showed that the n-alkanol effetcts at low concentrations were reversible as far the lipoidal pathway of the stratum corneum was concerned. These results demonstrate the general usefulness of this approach for evaluating the action of enhancers on the barrier function of the stratum corneum. It is suggested that the short chain alkanols may work at low concentrations as effective ‘fluidizing’ agents at some locus in the stratum corneum lipid bilayer at or near the polar head plane, but not in the deep bilayer hydrocarbon interiors.