PubMed1978
The skin is the most readily accessible organ of the human body; only a fraction of a millimeter separates its surface from the underlying capillary network. Yet, skin protects superbly against damage by micro- and macro-molecular entities, as well as against uncontrolled loss of vital biological substances, by virtue of its astonishingly low permeability to such substances. We have reexamined and attempted to reconcile the barrier characteristics of skin in terms not only of its composition and microstructure, but also of present understanding of membrane permeability and permselectivity. The principal barrier to percutaneous transport is localized within the stratum corneum. We have developed a mathematical model of this tissue as a two-phase protein-lipid heterogeneous membrane, which correlates the permeability of the membrane to a specific penetrant with the water solubility of the penetrant and with its lipid-protein partition coefficient. We have also found that a simplistic model of the sorption process, which invokes the coexistence of dissolved and mobile sorbed molecules in equilibrium with site-bound and immobile molecules within the membrane, accurately correlates experimental sorption data and transient transport measurements. The interstitial lipid phase of the stratum corneum is the cause of the exceedingly low, apparent diffusivity of drugs (e.g. scopolamine) and, in this regard, acts as the principal permeation barrier, whereas the drug sorbed by the stratum corneum is localized predominantly within the protein phase of the tissue. We have also found that the effects of the permeation adjuvant, dimethyl sulfoxide, on skin permeability are entirely consistent with accepted sorption-diffusion models of membrane transport, when changes in penetrant activity with changes in solvent composition and tissue microstructure induced by osmotic shock are properly allowed for.