Topical Peroxisome Proliferator-Activated Receptor Agonist Induces Molecular Alterations Enhancing Barrier Function and Water-Holding Capacity of the Human Stratum Corneum in Vivo

The peroxisome proliferator-activated receptor (PPAR) ligands modulate a variety of skin functions but are rarely used in cosmetics. The aim of this double-blind, placebo-controlled, in vivo study was to determine the effect of a topically applied 0.1% PPAR ligand on the composition and physiological parameters of the stratum corneum (SC). By comparing verum and placebo groups post-treatment, we demonstrate (via lipidomic analysis of tape strips) an unstatistically significant trend toward an increase in long-chain triacylglycerols (C50–C56) and medium- and long-chain ceramides (C42–C50) at the superficial SC. By comparing treated and untreated skin using confocal Raman microspectroscopy, we found that the changes in lipid composition in the verum group led to a significant increase in the number of trans conformers and orthorhombic organisation of lipids at the exemplary SC depth. An increase in unfolded states in the secondary and tertiary keratin structures results in an increased ability to bind water. The concentrations of tightly and strongly bound water increase, while weakly bound and unbound water decrease in the entire SC, indicating a transformation of water mobility to a state of increased hydrogen bonding. Thus, the topical PPAR ligands improve the water-holding capacity and the barrier function of the SC.