A fundamental investigation of surface-induced skin irritation

Abstract

Surfactants frequently come in contact with the skin in the form of personal care products, where they are used to improve the wetting and oil solubilizing qualities of the products. Surfactants are also known to induce skin irritation by damaging the barrier properties of the stratum corneum, the outer layer of the skin, and denaturing proteins in the epidermis and the dermis. The goal of this thesis has been to understand the relationship between the physicochemical properties of surfactant solutions and their skin irritation potential. In vitro tests were developed to measure: (1) the effect of surfactants on the barrier properties of the skin, (2) the concentration of surfactant in the skin, and (3) surfactant-induced protein denaturation, all of which can be related to skin irritation. The physicochemical properties of the surfactant solution, specifically, the concentration of the surfactant monomers (unmicellized surfactant), the composition of the surfactant monomers, and the size and shape of the surfactant micelles, were related to the results of these tests. An in vitro skin irritation test was developed that measures the electrical conductivity of pig skin to quantify the reduction in the barrier properties of the skin, or the skin damage, induced by surfactant solutions. Skin conductivity was found to be directly related to the transdermal water permeability, directly relating the skin conductivity to in vitro skin irritation. Skin conductivity was used to measure the in vitro skin irritation potential of mixtures of the anionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant dodecyl hexa(ethylene oxide) (C12E6), and a relationship was observed between the surfactant monomer concentration and

(cont.) the skin conductivity. The in vitro skin irritation test correctly ranked the in vivo irritation potential of three mild commercial soap bars-Dove, Lever 200, and Ivory. In order to understand the relationship between the micelle concentration and the surfactant-induced damage to the skin, a method was developed to measure the penetration of 14C-radiolabeled SDS surfactant into pig skin. It was found that both monomeric and micellar SDS are able to penetrate into the skin, and that the contribution of the micellar SDS to the concentration of SDS in the skin is comparable to the contribution of the monomeric SDS. SDS penetration into the skin was also measured in the presence of poly(ethylene oxide) (PEO), which forms PEO-bound SDS micelles, and C12E6, which forms SDS/C12E6 mixed micelles. In mixtures of PEO-bound and free SDS micelles, the PEO-bound SDS micelles were found not to penetrate into the skin while the free SDS micelles were found to penetrate. Mixing SDS with C12E6 led to a reduction in the penetration of SDS into the skin by reducing the SDS monomer concentration, as well as by reducing, or preventing altogether, the penetration of micellar SDS. The hydrodynamic radii of the free SDS micelles (21 A), the PEO-bound SDS micelles (25 A), and the SDS-C12E6 mixed micelles (24-30 A) were measured using dynamic light scattering. Based on these results, a new model of surfactant penetration into the skin was proposed, in which the penetration of micellar surfactant into the skin is limited by the size of the micelles...