Carbon dioxide ameliorates reduced desquamation in dry scaly skin via protease activation

Abstract Objective Scaling, a phenomenon showing an abnormal detachment of the stratum corneum (SC) owing to desquamation dysfunction, is commonly observed in various skin diseases or xerotic skin due to ageing and low humidity. Therefore, it is considered that ameliorating the disturbed desquamatory process of the SC leads to improvement in scaling. Carbon dioxide (CO 2 ) is known to be good for some skin diseases; however, the effect of CO 2 on scaling and its mechanism are not sufficiently clear. We aimed to elucidate the effect of transepidermal application of CO 2 on scaling and its mechanism of action. Methods Twenty healthy men with mild scaling on the cheeks were recruited for a double‐blind, placebo‐controlled, split‐face study. They applied the formulation containing CO 2 twice daily for 1 week. After the study, the SC was collected by tape stripping to analyse desquamatory protease activities and degradation of extracellular corneodesmosomes. Furthermore, the contribution of pH to proteolysis of the corneodesmosome by CO 2 was evaluated using three‐dimensional (3D) cultured epidermal models. Results The spectroscopic absorbance of tape strips, used as scaling indicators, was decreased, concomitantly with the amelioration of incomplete degradation of desmoglein‐1, one of the main corneodesmosomal proteins, and activation of trypsin‐like protease in the SC by transepidermal application of CO 2 . Experiments using 3D cultured epidermis showed that pH in the epidermal tissue was lowered by CO 2 , whereas a pH change was not observed with the application of the formulation containing hydrochloric acid, which was added to equalize the pH to that of the CO 2 formulation. Conclusion The transcutaneous application of CO 2 ameliorates reduced desquamatory process in xerotic skin, with concomitant mild acidification of the SC, thereby leading to improvement in scaling. Thus, CO 2 may have an advantage of efficiently and safely counteracting scaling of various skin disorders.