PEG-23 glyceryl distearate, a multifunctional skin-supporting material, upregulates the expression of factors associated with epidermal barrier and hydration.

OBJECTIVE: As the outermost organ of the human body, the skin plays a critical role in protecting against external agents and oxidative stress, as well as in preventing excessive water loss. Among its layers, the stratum corneum of the epidermis is central to both barrier function and moisture retention, with its structural integrity significantly influencing skin health and appearance. Polyethylene glycol-23 glyceryl distearate (GDS-23) can form niosomes, liposome-like structures with multiple layers and serve as a carrier in drug delivery systems (DDS). We previously reported that GDS-23 exerts multiple biological effects, suppressing inflammation and enhancing the endogenous antioxidant system via Nrf2 activation through phosphorylation of the autophagy adaptor protein p62. In this study, we investigated the effects of GDS-23 on epidermal barrier function and moisture retention using normal human epidermal keratinocytes (NHEKs) and a three-dimensional (3D) epidermal model, mimicking human skin structure. METHODS: NHEKs and the 3D epidermal model were treated with GDS-23. Gene expression in NHEKs was analysed using real-time polymerase chain reaction, while the levels of epidermal barrier- and moisture retention-related factors in the 3D model were evaluated using immunofluorescence staining. RESULTS: Treatment with GDS-23 upregulated the mRNA expression of genes involved in stratum cornea formation (filaggrin and loricrin), moisture retention (aquaporin 3 and hyaluronan synthase 3) and intercellular lipid synthesis (ceramide synthase, sulfotransferase 2B1 and peroxisome proliferator-activated receptor α) in NHEKs. Additionally, treatment with K67, which inhibits p62 phosphorylation and thereby suppresses Nrf2 activation via a non-canonical mechanism, suppressed the GDS-23-induced expression of filaggrin, loricrin, ceramide synthase, sulfotransferase 2B1 and aquaporin 3. In the 3D epidermal model, GDS-23 treatment upregulated the expression of Nrf2, downstream antioxidant factors and proteins involved in stratum corneum formation and moisture regulation. Mechanistically, GDS-23 enhanced endogenous antioxidant function and modulated the expression of molecular markers associated with epidermal barrier and moisture retention, thereby potentially contributing to skin homeostasis. CONCLUSION: As GDS-23 contributes to the maintenance of skin homeostasis, it is expected to have future applications in the cosmetic field and in the treatment of skin disorders. Overall, GDS-23 holds promise as a "multifunctional DDS material" that promotes skin health.