Alcohol effects on stratum corneum lipid thermotropic phase behavior

The stratum corneum is considered to be the diffusional barrier to water and other solute transport. The intercellular lipid multilayer domain is generally accepted as the lipophilic solute diffusional pathway. Thermal and short chain alcohol (ethanol, n-propanol, iso-propanol, and n-butanol) induced fluidization of the intercellular lipid domain has been implied to disrupt the barrier properties of the stratum corneum. Current investigations address the hairless mouse stratum corneum lipid thermotropic phase behavior in terms of lipid alkyl chain packing, mobility and conformational order as measured by Fourier transform infrared (FTIR) spectroscopy. A solid-solid gel phase transition is observed with an increase in the lipid chain mobility. The gel to liquid-crystalline phase transition follows near 65°C. The effects of short chain alcohols at iso-enhancement concentrations on the stratum corneum lipid alkyl chain packing, mobility and conformational order have also been investigated. No apparent effect of these alcohols on the solid-solid phase transition of the stratum corneum lipids was observed. Ethanol and n-propanol reduce the gel to liquid crystalline phase transition, while iso-propanol and n-butanol have no measurable effects. However, there was a reduction in the alkyl chain mobility in the densely packed gel phase lipids in the presence of ethanol and n-butanol. Ethanol induced interdigitation of phospholipid bilayers has been demonstrated in the literature. The effects of ethanol induced interdigitation of dipalmitoylphosphatidylcholine (DPPC) and distearoylphosphatidylcholine (DSPC) bilayer membranes on the FTIR spectral parameters were established in the current investigation. Similar effects on the FTIR parameters were observed in studies of the other alcohols with DSPC membranes, suggesting the possible induction of lipid chain interdigitation. Based on the model membrane data, the ethanol and n-butanol induced reduction in the stratum corneum lipid chain mobility was suggested to results from limited regions of lipid chain interdigitation. Possible mechanistic relationships between the current FTIR spectroscopic results with available literature data of thermally and alcohol induced lipophilic solute penetration enhancement through skin are discussed.