The research found that GDS-23 activated key molecular pathways in skin cells and a three-dimensional (3D) epidermal model, leading to higher expression of proteins critical for hydration and structural integrity.
This showed it was not only a delivery material, but also a skin-supporting agent that could directly promote epidermal health.
From drug delivery to multifunctional skin active
PEG lipids such as GDS-23 are known for their ability to form niosomes, vesicles similar to liposomes but more stable and cost-effective. These structures have traditionally been used in drug delivery systems (DDS).
Past studies had shown that GDS-23 could suppress inflammation and enhance antioxidant defences by activating the transcription factor Nrf2, a master regulator of cellular protection against oxidative stress.
The new study expanded on these findings by showing that GDS-23 could also boost epidermal barrier-related proteins and moisture-regulating molecules.
In this case, the novelty was that GDS-23 was able to upregulate genes and proteins involved in both barrier formation and hydration, suggesting cosmetic as well as therapeutic applications.
Study design
The team treated normal human epidermal keratinocytes (NHEKs) with GDS-23 and monitored gene expression through real-time polymerase chain reaction. They also applied GDS-23 to a 3D epidermal model designed to mimic the structure and function of human skin.
They then analysed markers related to barrier formation (filaggrin and loricrin), lipid synthesis (ceramide synthases and sulfotransferase 2B1), and hydration (aquaporin 3 and hyaluronan synthase 3).
They also evaluated antioxidant proteins linked to Nrf2 signalling using immunofluorescence staining.
Key findings
The results showed that GDS-23 triggered a broad range of positive changes in skin biology, particularly in barrier proteins, hydration molecules, lipid synthesis enzymes and antioxidant defence.
Filaggrin and loricrin, structural proteins crucial for the stratum corneum, were strongly upregulated. These proteins help maintain firmness, reduce allergen penetration, and generate natural moisturizing factors.
At the same time, aquaporin 3 (which transports water and glycerol across keratinocyte membranes) and hyaluronan synthase 3 (which drives hyaluronic acid production) were significantly increased.
Additionally, the researchers found that ceramide synthases (CerS2 and CerS3) and sulfotransferase 2B1 were elevated, supporting the production of ceramides and sulphated cholesterol, essential lipids for barrier integrity.
Furthermore, in the 3D model, GDS-23 boosted Nrf2, along with its downstream targets NAD(P)H-quinone oxidoreductase (NQO1) and heme oxygenase-1 (HO-1).
When researchers blocked Nrf2 activation using the inhibitor K67, the effects of GDS-23 on several targets — including filaggrin, loricrin, aquaporin 3, and ceramide-related genes — were suppressed.
These results indicate that GDS-23 enhanced both barrier and hydration functions by modulating Nrf2-dependent and PPARα-dependent pathways.
Implications for cosmetics and dermatology
The findings suggested that GDS-23 may have wide-ranging applications across cosmetics, functional skincare, and dermatology.
By improving skin hydration and barrier strength, the ingredient could support healthy ageing and resilience against environmental stressors, such as UV exposure and pollution.
In addition, its ability to activate Nrf2 and enhance antioxidant responses could make it valuable in addressing oxidative stress-driven conditions like atopic dermatitis, psoriasis, and ichthyosis.
GDS-23-induced upregulation of filaggrin and loricrin expression may also represent a novel therapeutic option for maintaining skin homeostasis and treating skin diseases in the future.
Mechanism of action
The study provided insights into how GDS-23 achieved its multifunctional effects, highlighting three key mechanisms — Nrf2 activation via p62 phosphorylation, lipid metabolism through PPARα, and moisture regulation.
In the first instance, GDS-23 phosphorylated the adaptor protein p62, preventing it from binding Keap1 and freeing Nrf2 to enter the nucleus and switch on protective genes.
When it comes to lipid metabolism, GDS-23 also upregulated peroxisome proliferator-activated receptor alpha (PPARα), a regulator of lipid production in the skin. This in turn supports ceramide synthesis and barrier repair.
Finally, GDS-23 increased aquaporin 3 and hyaluronan synthase 3 expression that ensured water and glycerol transport, along with hyaluronic acid production; this improved hydration and wound healing capacity.
These mechanisms indicated that GDS-23 did not simply act as a carrier, but directly supported the biological processes that kept skin healthy.
Industry opportunities
For manufacturers and suppliers, the multifunctionality of GDS-23 could be particularly appealing. As a PEG lipid, its ability to combine the stability and delivery advantages of niosomes with intrinsic skin health benefits could make it a potential next-generation cosmetic active.
The authors suggested that with interest in multifunctional ingredients growing, GDS-23 could offer formulators a way to combine delivery efficiency with direct biological activity.
As consumer demand for products addressing both barrier repair and hydration is rising, especially in Asia-Pacific where sensitive skin and dryness are common concerns, GDS-23 could meet multiple consumer needs in a single formulation by also offering antioxidant and anti-inflammatory support.
Limitations and next steps
The study was conducted in cell cultures and a lab-based 3D skin model rather than in human clinical trials. While the molecular results were promising, the researchers acknowledged the need for in vivo studies to confirm efficacy and safety in actual skin applications.
Future research will also need to clarify whether GDS-23 acts directly as a PPARα agonist or indirectly through Nrf2. Understanding these mechanisms could guide optimised formulations for cosmetics and therapeutic products.
Despite these limitations, the study provided a strong foundation for the use of GDS-23 in multifunctional skin care.
The researchers concluded: “These results suggest that GDS-23 may be beneficial in the management of skin conditions such as atopic dermatitis, psoriasis, and ichthyosis.
“As a member of the PEG lipid family, GDS-23 has potential application in multifunctional DDS as a therapeutic agent for improving transdermal drug absorption, enhancing endogenous antioxidant function, as well as strengthening epidermal barrier function and moisture retention to maintain skin homeostasis and facilitate wound healing.”
Source: International Journal of Cosmetic Science
“PEG-23 glyceryl distearate, a multifunctional skin-supporting material, upregulates the expression of factors associated with epidermal barrier and hydration”
https://doi.org/10.1111/ics.70005
Authors: Tatsuro Miyoshi, et al.
