Abstract

Hyaluronic acid (HA) is widely used in skincare, but its efficacy varies with molecular weight (MW), affecting its skin penetration and activity. This study examined whether HA20, a broad-MW HA complex (weight-average MW: 188 kDa, 10–1000 kDa), improves skin absorption and shields human skin models from environmental stress. HA transepidermal bioavailability, extracellular-matrix responses, glyoxal-induced Nε-(carboxymethyl)lysine (CML), UVA-induced mitochondrial membrane potential (MMP) loss, Th2 cytokine-induced markers, and dryness-induced barrier changes were assessed in reconstructed human epidermis, dermal fibroblasts, and epidermal keratinocytes. HA20 exhibited greater apparent permeation detectable by ELISA at all time points during the 24 h RHE assay compared to high-MW HA. In fibroblasts, 0.05% HA20 increased type I collagen secretion from 535.20 to 585.47 pg/mL and elastin from 8.68 to 9.24 pg/mL, reduced CML fluorescence to 70.13% of the glyoxal control, and increased MMP-associated fluorescence from 58.76% in the UVA model group to 298.86%. In keratinocytes, 0.1% HA20 reduced IL-4/IL-13-induced NELL2 and CAII expression. Under acute dryness, HA20 maintained stratum corneum morphology and altered transcriptomic signatures related to epidermal differentiation, extracellular matrix organization, and barrier-associated genes, including KRT37, COL7A1, ACER2, and SPRR1A. These findings suggest that HA20 supports barrier resilience mainly through improved transepidermal delivery and ECM or barrier-repair responses.

Keywords