Mechanism of the Enhancement Effect of n‐Octyl‐β‐D‐thioglucoside on the Transdermal Penetration of Fluorescein lsoiliocyanate-Labeled Dextrans and the Molecular Weight Dependence of Water-Soluble Penetrants through Stripped Skin

To clarify the mechanism of the enhancing effect ofn‐octyl‐β‐D‐thioglucoside (OTG), which acts as a potent enhancer for skin penetration of peptides and water‐soluble penetrants, the in vitro penetration of macromolecules [fluorescein isothiocyanate‐labeled dextrans (FTIC‐dextrans)] was evaluated with hairless rat skin and stripped skin. The FITC‐dextrans (MW, 4400, 9600, and 69 000 Da, referred to as FD‐4, FD‐10, and FD‐70, respectively) penetrated more easily in the presence of OTG (1.5%), with high fluxes equivalent to those through stripped skin. This result indicated that the enhancement effect of OTG on the penetration of macromolecules through the stratum corneum was extensive, and the barrier function of the corneum was nearly eliminated by the OTG treatment. OTG significantly solubilized the stratum corneum proteins and ceramides during the initial time stage. Scanning electron microscopic observations demonstrated that OTG treatment dramatically changed the cell membrane (i.e., exfoliation of cell membranes and dissociation of adherent cornified cells), suggesting a significant disturbance of the cohesive laminae and barrier functions. The extent of dissociation of cell membranes increased with treatment time, without significant changes in the cell junctions. These results clarify that the enhancement mechanism of OTG was different from that of laurocapram and other lipophilic enhancers. The permeability of polar solutes with differing molecular sizes (MW, 180–69 000 Da) through stripped skin was size dependent (r = 0.997, p < 0.001). However, the viable epidermis and dermis restricted the penetration of macromolecules, such as FD‐70.