Binding of Drugs to Human Skin: Influencing Factors and the Role of Tissue Lipids

Abstract

For a series of ten drugs with different physicochemical properties, binding to human skin (epidermis and corium) was determined. Epidermis was obtained by suction blistering, and corium was sliced with a microtome (0.2 mm). Binding experiments were performed in dialysis chambers, containing labelled drug solutions. All drugs investigated were bound to epidermis and corium. With one exception, epidermal drug binding was significantly higher than corial binding. Nevertheless, a good correlation between binding of drugs to both skin fractions could be found. In a range from 10−7 to 10−3 mol L−1 binding of drugs to both skin fractions is linear and not saturable. A good correlation was found between binding and lipophilicity of drugs, determined as the partition coefficients between an organic phase (octanol or heptane) and phosphate buffer of pH 7.0. The results show that binding to epidermis and corium is not saturable and depends on lipophilicity of drugs, indicating unspecific binding. Further binding experiments were performed with lipid-depleted tissue. Since drug binding to lipid-depleted samples and control samples differ only to a moderate extent, it is suggested, that tissue lipids play a marginal role on drug binding. Hence, drugs are bound to human skin by other components like proteins.