ENHANCED PERMEATION OF POLAR COMPOUNDS THROUGH HUMAN EPIDERMIS .1. 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 per meation mechanisms. Both thermodynamic and kinetic variables associate d with the enhanced permeation of mannitol were ascertained in the pre sence of high concentrations of short chain alcohols. Permeation of ma nnitol through human epidermis in the presence of 75% (v/v) alcohol-sa line mixtures was determined in symmetric, side-by-side diffusion cell s at 32 degrees C. Permeability coefficients increased with increasing alcohol chain length (iso-propanol > ethanol > methanol). Uptake of m annitol into the epidermal tissue increased in the presence of the sho rt chain alcohols, but was independent of alcohol chain length. In add ition, mannitol solubility decreased in the presence of the short chai n alcohols, but again was independent of alcohol chain length. Therefo re, increased mannitol permeability with increasing alcohol chain leng th could not be attributed to thermodynamic variables. Changes in the amount and conformation of stratum corneum lipids and proteins were de termined by Fourier transform infrared (FTIR) spectroscopy. Stratum co rneum lipid conformation and mobility was not significantly altered in the presence of the short chain alcohols. However, decreased absorban ce 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 in frared 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 permeati on and extraction of lipids as well as proteins from human skin in the presence of 75% (v/v) aqueous alcohol solutions.