Enhancing Skin Penetrability of Hyaluronic Acid through Physicochemical Property Control for Improving Effects

Hyaluronic acid (HA) is renowned for its excellent moisturizing properties, demonstrating remarkable potential for preserving youthful and vibrant skin. Our previous study using magnesium chloride hexahydrate (MgCl2) -incorporated HA (HA-Mg) demonstrated significantly improved penetrability of high molecular weight HA into the stratum corneum (SC). However, the effects of this penetration beyond simple moisturization remain unexplored. In addition, the presence of MgCl2 reduced the bound water near the HA molecules, thereby affecting their moisturizing capacity─an observation attributed to the shielding effect on carboxyl groups. In this study, we engineered a new method aimed at improving the moisturizing effect of HA-Mg after topical application and clarified the usefulness of SC-penetrated HA. SC viscoelasticity and transparency were measured using a dynamic viscoelasticity device and haze meter, respectively. Next, the effect of chelating agents on specific volumes of HA-Mg molecules was investigated. While bound water contents were measured using a differential scanning calorimeter (DSC), the effect of chelating agents on the moisturizing effect of HA and skin texture were assessed using a Corneometer® and digital microscope, respectively. HA-Mg application resulted in reduced SC elasticity but increased transparency. MgCl2 addition induced a decreased HA's specific volume, whereas adding chelating agents, particularly sodium metaphosphate (SMP), yielded an improved HA-Mg's specific volume. DSC measurements showed increased bound water content in HA-Mg upon SMP addition. In addition, post-HA-Mg application, in vivo SMP treatment yielded elevated SC water content and a young-like uniform skin texture. Overall, this approach can noninvasively introduce natural HA into the skin without compromising its effectiveness while supporting youthful skin in daily care.