Abstract

Infrared (IR) spectroscopy is one of the most chemically specific analytical methods that gives information about composition, structure, and interactions in a material. IR spectroscopy has been successfully applied to study the permeation of xenobiotics through the skin. Combining IR spectroscopy with an IR array detector led to the development of Fourier transform infrared (FTIR) spectroscopic imaging, which generates chemical information from different areas of a sample at the microscopic level. This is particularly important for heterogeneous samples, such as skin. Attenuated total reflectance [corrected] (ATR)-FTIR imaging has been applied to measure, in situ, the diffusion of benzyl nicotinate (BN) through the outer layer of human skin [stratum corneum (SC)]. In vitro experiments have demonstrated the heterogeneous distribution of SC surface lipids before the penetration of a saturated solution of BN. Image analysis demonstrated a strong correlation between the distribution of lipids and drugs, while ethanol appeared to be homogenously distributed in the SC. These results show the ability of ATR-FTIR imaging to measure simultaneously the affinities of drug and solvent to the lipid-rich and lipid-poor skin domains, respectively, during permeation. This information may be useful in better understanding drug-diffusion pathways through the SC.

Highlights

  • Human skin is a naturally efficient barrier that protects the body from physical and chemical “onslaught.”[1] The first layer of our skin is a barrier to most molecules; the skin can be used as a route to deliver drugs systemically

  • The stratum corneumSC, which is the outer skin layer with a thickness of ϳ10 to 20 ␮m, is a structure of dead and anucleate cellscorneocytessurrounded by a lipid matrix that can be visually described as a “brick and mortar” model

  • This study demonstrated the possibility of measuring SC heterogeneity by observing lipidrich and lipid-poor regions, and the permeation and distribution of a model drug and solvents into the SC

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Summary

Introduction

Human skin is a naturally efficient barrier that protects the body from physical and chemical “onslaught.”[1] The first layer of our skin is a barrier to most molecules; the skin can be used as a route to deliver drugs systemically. The stratum corneumSC, which is the outer skin layer with a thickness of ϳ10 to 20 ␮m, is a structure of dead and anucleate cellscorneocytessurrounded by a lipid matrix that can be visually described as a “brick and mortar” model. Molecules can use an intracellular pathwaythe “brick”͒ and/or intercellular pathwaythe “mortar”͒ to diffuse through the SC.[2,3,4] The lipid bilayers surrounding the SC cells provide a key way of controlling the drug flux. The organization of the lipid matrix may be sensitive to any perturbation, such as temperature.[5,6] or chemical absorption.[7]

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