INTERACTIONS OF NONIONIC SURFACTANT VESICLES WITH CULTURED KERATINOCYTES AND HUMAN SKIN INVITRO - A SURVEY OF TOXICOLOGICAL ASPECTS AND ULTRASTRUCTURAL-CHANGES IN STRATUM-CORNEUM

The inhibition of cell proliferation of SV-40 transformed human keratinocytes was used as a model substrate to determine the dermal toxicity of formulations containing non-ionic surfactant vesicles (NSVs). Both the effects of the molecular structure of the surfactant (polyoxyethylene alkyl ethers/esters) and the incorporation of cholesterol on the cell proliferation were investigated. The alkyl chain length as well as the length of the polyoxyethylene headgroup had only a minor effect on the proliferation of the keratinocytes. However, the bond by which the alkyl chain was linked to the polyoxyethylene headgroup (i.e. an ether or an ester bond) had a strong influence on the cell proliferation. The concentration of the surfactants that inhibited cell proliferation by 50% was for the ether surfactants 10-fold lower than for the ester surfactants. The cholesterol content of the bilayers had no effect on the cell proliferation. These results are compared with those obtained in earlier studies, where the effect of surfactants on the ciliary beat frequency was determined (a model used to determine the toxicity of intranasal formulations). Furthermore, the interactions between NSVs and excised human skin were determined after 48 h of incubation under occlusion. Freeze-fracture electron microscopy revealed that the vesicles were able to introduce changes in the ultrastructure of the intercellular lipid lamellae of the stratum corneum down to a depth of approximately 10-mu-m.