The ingredient, called Caffeoyl hexapeptide-9 (CH-9), is a hybrid molecule that offers superior stability, skin penetration, and clinical results in restoring skin firmness.
The study was conducted by Shenzhen Winkey Technology, P&G Singapore Innovation Center, and Nanyang Technological University.
It demonstrated how peptide-drug conjugate (PDC) technology could solve long-standing hurdles in skin care formulation, such as poor peptide absorption and antioxidants’ chemical instability.
Bridging the gap between peptides and small molecules
Traditional skin care often relies on two separate categories of actives: peptides and small-molecule antioxidants.
While peptides like Hexapeptide-9 (H-9) are excellent at signalling the skin to produce collagen, they are often fragile and struggle to penetrate the skin barrier. Conversely, small molecules like caffeic acid (CA) are potent antioxidants but are notoriously unstable in water, and turn brown quickly in cosmetic bottles.
To address these limitations, the researchers covalently linked H-9 and CA to form a single “conjugate” molecule. This process involved a convergent solid-phase peptide synthesis strategy, ensuring the final ingredient reached a purity level of at least 95%.
PDC technology has been used in pharmaceuticals to improve drug delivery but has not been widely explored in the personal care industry.
The researchers noted that CH-9 combined the targeting power of peptides with the bioactive functions of small molecules, which overcame the traditional trade-off between efficacy and delivery.
Superior protection against UV damage
The study put CH-9 to the test against its parent peptide, H-9, using human skin cells exposed to ultraviolet B (UVB) radiation. While UVB exposure typically reduces cell viability and destroys collagen, CH-9 showed a remarkable ability to rescue the skin.
In laboratory models using human keratinocytes and fibroblasts, CH-9 restored the levels of collagen types I, III and IV, whereas H-9 only significantly improved collagen type IV.
Notably, at higher concentrations, CH-9 promoted the proliferation of skin cells in models challenged by UV light, highlighting its potential for use in formulations designed for intensive skin repair and regeneration.
Furthermore, CH-9 displayed a direct antioxidant shield, which H-9 lacked. Using two different chemical assessments — DPPH and ORAC assays — the team proved that CH-9 could successfully scavenge hydroxyl and peroxyl radicals.
These free radicals are the primary culprits behind oxidative stress, which causes the breakdown of the skin’s structural integrity over time.
Fighting inflammation at cellular level
Beyond collagen production, the researchers investigated how the new molecule handled the inflammatory “firestorm” caused by solar radiation.
When exposed to UV rays, skin releases pro-inflammatory cytokines like interleukin-6 (IL-6) and interleukin-8 (IL-8), which accelerate the ageing process. This phenomenon is often called “inflammageing”.
In 3D full-thickness skin models, treatment with CH-9 significantly reduced the release of these inflammatory markers. In contrast, the parent peptide H-9 showed no significant inhibitory effect on these specific cytokines.
The study suggested that CH-9 achieved this by suppressing the NF-κB pathway, a master switch for inflammation in human cells. By keeping this switch in the “off” position, CH-9 could prevent the damage that typically follows a day in the sun.
Deeper penetration and formulation stability
One of the study’s most significant breakthroughs was the improvement in how the ingredient behaved — both in the bottle and on the skin.
Peptides are often too “water-loving” to pass through the skin barrier’s oily layers easily. By attaching the caffeoyl group, the researchers modified the molecule’s physical properties to make it more compatible with the skin’s surface.
Using molecular dynamics simulations, the team observed that the caffeoyl moiety allowed the molecule to insert itself more deeply and stably into the stratum corneum. The Raman spectroscopy tests on human volunteers confirmed this.
Within just 30 minutes of application, CH-9 reached significantly higher concentrations in the skin compared to the standard H-9 peptide, proving that the chemical modification acted as a “passport” for deeper delivery.
One of the biggest issues with natural antioxidants like caffeic acid is their tendency to oxidise. While pure caffeic acid can cause cosmetic serums to discolour and turn a muddy brown under heat stress, the CH-9 conjugate remained clear and stable.
This suggested that the new ingredient would be far easier to work with in high-performance, water-based formulations that require a long shelf life.
Clinical results confirm firmer skin
In addition, the researchers conducted a 28-day double-blind clinical trial involving 96 women aged 40 to 55. Participants applied a formulation containing 50μg/mL of either CH-9, H-9, or a placebo twice daily.
The results showed that CH-9 was significantly more effective at improving skin density and elasticity. By the end of the four-week period, the CH-9 group saw a 32.17% improvement in gross elasticity and a 30.60% increase in skin firmness. These figures were more than double the improvements seen in the group using the parent peptide H-9.
Ultrasonic imaging further supported these findings, revealing a visible increase in dermal density signals in the skin of those using CH-9. The researchers attributed this to the molecule’s ability to protect the basement membrane and prevent degradation of the extracellular matrix.
A new standard
The study suggested that CH-9’s anti-photoageing mechanism was multi-faceted, with its results serving as a proof of concept for using PDC technology to create multifunctional actives.
Molecular docking simulations indicated that the molecule fit perfectly into the catalytic domain of MMP2, an enzyme responsible for breaking down collagen. By physically blocking this enzyme and neutralising oxidative stress simultaneously, CH-9 provided a dual-action defence against environmental ageing.
By chemically modifying existing peptides with stable antioxidant groups, cosmetic companies can potentially offer products that penetrate deeper and perform better without the stability issues that plague traditional formulations.
As the beauty industry seeks more sophisticated ways to tackle UV damage, hybrid molecules like CH-9 represent a promising shift toward precision-engineered cosmetic chemistry.
Source: Cosmetics
“Development of a Novel Peptide-Caffeic Acid Conjugate with Enhanced Anti-Photoaging Properties: Efficacy, Transdermal Permeation, and Stability”
https://doi.org/10.3390/cosmetics13010024
Authors: Liu Lijuan, et al.
