Liposomal Hyaluronic Acid Enhances Skin Permeation and Hydration: Evidence from In Vitro, Ex Vivo, and In Vivo Studies

Topically applied hyaluronic acid (HA) hydrates the skin without efficient penetration. This study compared the penetration efficiency of liposomal hyaluronic acid (LPS-HA) against that of conventional HA across different models. Dynamic light scattering revealed that particles of LPS-HA (226.1 nm, PDI 0.2898) were smaller than those of HA (798.4 nm, PDI 0.8709). In Strat-M® membrane assays, permeability over 24 h was higher with LPS-HA (629.37 ± 103.26%) than that of HA (508.04 ± 93.80%; <i>p</i><0.05). In keratinocytes, LPS-HA increased differentiation markers filaggrin and caspase-14 in a concentration-dependent manner, with maximal induction at 1% (186.6 ± 6.99% and 249.3 ± 8.60%) <i>vs</i>. HA (117.9 ± 7.64% and 130.1 ± 2.90%; <i>p</i><0.05). In fibroblasts, LPS-HA increased the expression of type I and type III collagens (138.4 and 133.6%) without increasing that of elastin (68.3-94.7%) and reduced UVB-induced IL-6 (79.1-90.2% of UVB; <i>p</i><0.05). <i>Ex vivo</i>, LPS-HA enhanced HAS-3 mRNA (3.03 ± 0.19-fold <i>vs</i>. 1.31 ± 0.13-fold with HA; <i>p</i><0.05) and increased epidermal hyaluronan staining. In PM10-treated human skin, LPS-HA reduced inflammatory cytokines (TNF-α, IL-6, IL-8, and IL-1β) and suppressed mast cell degranulation, similar to dexamethasone, and reduced ROS formation (124.46 ± 8.45% <i>vs</i>. 169.35 ± 9.40% in PM10-only, <i>p</i><0.01) without histological abnormalities. In a 20-subject clinical study, corneometric hydration with LPS-HA was higher than that of control (96.99% <i>vs</i>. 36.31%; RM-ANOVA, <i>p</i><0.001). Collectively, LPS-HA enhanced skin permeation, hydration, and anti-inflammatory responses, supporting its potential as a cosmetic moisturizing ingredient.