Investigation of the mechanism of transdermal penetration enhancer: a comparison of multiphoton microscopy and electron microscopy

The aim of this study is to characterize the ability of multiphoton microscopy in monitoring the transdermal penetration enhancing effect of a depilatory agent and the associated structural alterations of stratum corneum. The result is compared with the electron microscopic findings. Our results show that the penetration of both hydrophilic and hydrophobic agents can be enhanced. The morphology of corneocytes becomes a homogenized pattern with focal detachment of surface corneocytes. In combination with Nile red staining, multiphoton imaging also shows that the regular motar-like distribution of lipid matrix was disrupted into a homogenized pattern of lipid distribution. These results are well correlated with the findings of ultrastructural analysis by electron micrographs showing disintegration of the protein envelope of coenocytes, disruption of intracellular keratin and loss of the regular lamellar packing of intercellular lipids. We conclude that, in addition to quantifying the permeation profiles of model drugs, multiphoton microscopy is able to detect the penetration enhancer-induced structural alterations of stratum corneum.