Enhanced permeation of polar compounds through human epidermis. I. Permeability and membrane structural changes in the presence of short chain alcohols.

The influence of alcohol chain length on polar compound permeation in human skin was investigated to further understand alcohol-enhanced permeation mechanisms. Both thermodynamic and kinetic variables associated with the enhanced permeation of mannitol were ascertained in the presence of high concentrations of short chain alcohols. Permeation of mannitol through human epidermis in the presence of 75% (v/v) alcohol-saline mixtures was determined in symmetric, side-by-side diffusion cells at 32 degrees C. Permeability coefficients increased with increasing alcohol chain length (iso-propanol > ethanol > methanol). Uptake of mannitol into the epidermal tissue increased in the presence of the short chain alcohols, but was independent of alcohol chain length. In addition, mannitol solubility decreased in the presence of the short chain alcohols, but again was independent of alcohol chain length. Therefore, increased mannitol permeability with increasing alcohol chain length could not be attributed to thermodynamic variables. Changes in the amount and conformation of stratum corneum lipids and proteins were determined by Fourier transform infrared (FTIR) spectroscopy. Stratum corneum lipid conformation and mobility was not significantly altered in the presence of the short chain alcohols. However, decreased absorbance of the alkyl chain suggested lipid extraction, which increased with increasing alcohol chain length. Stratum corneum protein conformation was altered in the presence of the short chain alcohols. Decreased infrared absorbance of the Amide I band maximum suggested extraction of stratum corneum proteins, which increased with increased alcohol chain length. These results suggest a correlation between enhanced permeation and extraction of lipids as well as proteins from human skin in the presence of 75% (v/v) aqueous alcohol solutions.