Permeation of hyaluronan tetrasaccharides through hairless mouse skin: an in vitro and in vivo study

Hyaluronan (HA) is a well-known active ingredient for cosmetic and drug applications. However, based on its varying molecular size, HA may have limited skin permeation. Therefore, the aim of the present study was to investigate the in vitro skin permeability of HA tetrasaccharide (HA4). In addition, the effects of HA4 on in vivo skin barrier function were examined. The cumulative amounts of HA4 through stratum corneum (SC)-stripped skin and full-thickness skin after 8 h were 2,109.6 and 0.8 μg/cm², respectively. Furthermore, the cumulative amounts of HA4 permeated after 8 h were 784.4 ng/cm² for a HA4 solution with a pH 4 and 70.0 ng/cm² with a pH 7 on full-thickness skin. Next, the in vivo effects of HA4 on the water content of the SC and transepidermal water loss (TEWL) were investigated. The dorsal skins of hairless mice were irradiated to a UVA dose of 22.3 J/cm²/d, 5 times a week. In the control group, the water content of the SC was decreased and TEWL and epidermal thickness were increased with UVA irradiation than the normal group. However, the water content of the SC was increased in the HA4 group than that of the control group in the non-UVA irradiation groups. In addition, the water content of the SC was increased and TEWL and epidermal thickness were decreased in the HA4 group than those of the control and HA groups. These results suggest that treatment with HA4 improved skin functional recovery after UVA irradiation by skin penetration of HA4.