Petroselinic Acid and Oleic Acid: Comparison of Enhanced Skin Permeability Relative to Affinity for Saturated Fatty Acids of Stratum Corneum

Abstract

We have previously shown that cis-unsaturated fatty acids dissolved in propylene glycol (PG) directly alter the lipid structure of the stratum corneum, subsequently enhancing the transfer of PG into the dermis. In turn, PG disorders the protein structure of the dermis by using fourier infrared transform/attenuated total reflection (FT-IR/ATR) analysis. The present study evaluates the skin permeability of indomethacin (IM) and PG enhanced by petroselinic and oleic acids in vitro and in vivo in rat. Petroselinic acid enhanced the permeability of IM and PG more than oleic acid did. This was consistent with the degree of skin structure alternation caused by petroselinic acid and oleic acid. To differentiate petroselinic acid from oleic acid as the skin penetration enhancer, we examined the stability of cis-unsaturated fatty acids in constituents of the stratum corneum by calculating the interaction energy, using molecular mechanics analysis. Palmitic acid and stearic acid were chosen as model compounds, since these fatty acids contributed to the increased lipid fluidity of the stratum corneum as the constituents. The results of calculations when using a molecular model with an optimized structure indicated that the energy difference, ΔE, between cis-unsaturated and saturated fatty acids was negative in each of the combinations and that petroselinic acid was more potent than oleic acid in interacting with saturated fatty acids. These data suggest that the ability of petroselinic and oleic acids to evaluate skin permeability depend on the affinity for the constituents of the stratum corneum.