Abstract
Non-invasive delivery of hyaluronan into the stratum corneum (SC) is extremely difficult because of its high molecular weight and the strong barrier of the SC. We developed a safe method of administering hyaluronan into the human SC and determined its penetration route. The amount of hyaluronan that penetrated into the SC was 1.5-3 times higher in the presence of magnesium chloride hexahydrate (MgCl2) than other metal chlorides. The root-mean-square radius of hyaluronan in water decreased with the addition of MgCl2. Moreover, MgCl2 solutions maintained their dissolved state on a plastic plate for a long time, suggesting that size compaction and inhibition of hyaluronan precipitation on the skin enhanced hyaluronan into the SC. Our results also strongly suggest that an intercellular route contributes to the penetration of hyaluronan from the upper to the middle layer of the SC. No disruption to the SC barrier was observed after continuous use once a day for 1 month, demonstrating the potential of our method for the safe, topical application of hyaluronan.