24 SKIN CARE
and a 50% reduction in pinch recoil timing by week 12. Taken in totality, familiar peptides present opportunities to handle Ozempic face both from a preventative standpoint and, to some degree, a topical treatment standpoint as well.
Miniproteins Miniproteins are a new technology for cosmetics that have branched off from the pharmaceutical industry. Their amino acid sequence is significantly longer than traditional peptides, which allows them to fold. The folding process enhances stability, enhances efficacy, and significantly reduces the volume so that miniproteins may penetrate into the skin.
These properties allow miniproteins to
transcend the capabilities of peptides and solve some of their limitations. For instance, peptides are open to degradation by proteases and unable to bind many receptors due to their lack of tertiary structure. Miniproteins are more resistant to degradation, which allows for a longer term response in the skin and their 3D folded conformation allows for interactions that were previously impossible. Compared to the wound-healing peptide discussed prior, miniproteins that activate wound healing mechanisms are also promising actives for ameliorating crepey skin. For example, XEP 716 is a miniprotein that mimics TGFB (Transforming Growth Factor Beta), which is a common ‘anti-ageing’ target and wound healing signalling compound naturally in skin. TGFB is a potent inducer of collagen, elastin, and hyaluronic acid production. Impaired TGFB signaling can contribute to the appearance of saggy, wrinkled, fragile skin.10 The clinical efficacy of this miniprotein
was evaluated on 25 subjects of 40-60 years age using a randomized, double-blind half face study where the vehicle was used as the control. Obtaining a statistically significant result under these conditions is a formidable task since many extraneous variables are accounted for. Despite this, the miniprotein provided significant increases in dermal density, thickness, firmness, and achieved visually younger looking skin (measured by Visia-CR and professional assessors) in just one month of treatment.10 Miniproteins present an intriguing avenue
of innovation for future cosmetic treatments. They also disrupt traditional notions of skin penetration, such as the 500Da rule which states that substances above 500Da do not penetrate deep into skin. Miniproteins as large as 2kDa have exhibited penetration through the epidermis via EpiSkin modelling and even through reticular dermal layers via human skin explant data, fluorescent staining data, and clinical efficacy. In summary, miniproteins are a promising
new frontier for cosmetics and ‘wound-healing miniproteins’ present a potentially superior solution to crepey skin than wound-healing peptides. As expected, they are also multi- fold more expensive than peptide solutions, which give both options a place in the current cosmetics market.
PERSONAL CARE February 2025
Figure 7: Patch test results of a subject exposed to 0.5% hydroxypinacolone retinoate (left) compared to 0.5% retinol (right). Increased redness for retinol condition indicates higher irritation than HPR
Bakuchiyl Salicylate 4ug/mL PhytoCuticle
Gene (Symbol) HaS3 AQP3 ΔF 3.2 2.1 P-Value 0.001 0.017 Bakuchiol 4ug/mL ΔF 1.3 1.6 P-Value 0.317 0.019 Retinol 50C 4ug/mL ΔF 1.2 2.5 P-Value 0.5 6.00
Figure 8: Gene expression assay results of human keratinocyte cell cultures (HaCaT) exposed to bakuchiyl salicylate, bakuchiol, and retinol. The markers of interest were Hyaluronan Synthase 3 (HaS3) and Aquaporin 3 (AQP3), both key markers for skin hydration. Retinol did not exhibit statistically significant changes in any of them. Bakuchiol exhibited statistically significant increase in AQP3. Bakuchiyl salicylate was the only active to show highly significant increases in both HaS3 and AQP3
Retinoids If active technologies were a rock band, retinoids would be the star. This is clear given their history of treating acne, hyperpigmentation, psoriasis, alongside their anti-ageing benefits as well (collagen production, turnover regulation, etc.). By maintaining the quality of skin with consistent use, retinoids have been used as stretch mark treatments as well in multiple clinical studies.11 Similarly, they are the benchmark active
in treating crepey skin as well, both as a preventative measure to avert age-related decline and as a potential treatment to firm up crepey skin. The prescription drug form of retinoic
acid is Tretinoin. In cosmetics, derivatives of retinoid acid are used (like retinol) which must be converted to retinoic acid through multiple enzymatic steps to exert their activity. This is done to mitigate the irritation associated with Tretinoin. However, next-generation retinoid treatments have entered the cosmetics industry that do not need enzymatic conversion to have efficacy and retain a mildness profile even better than retinol. Granactive Retinoid Pro+ is an encapsulated
form of HPR (short for hydroxypinacolone retinoate: a retinoic acid ester), which touts these benefits while offering a timed release
mechanism as well. The encapsulation allows for a robust stability profile (photostable, temperature stable, oxidative protection), which can increase treatment adoption. With each successive innovation in retinoid
technologies, the use cases expand as limiting factors (irritation, photostability, formulation types) subside. This helps break down barriers to treatment and streamline consistent use.
Bakuchiol
Bakuchiol is a plant derived compound with efficacy similar to retinoids in that it can bind the same retinoic acid receptor types. This coincides with modern trends of ‘natural’ beauty. The logic behind their incorporation in saggy skin treatments is largely the same as retinoids: maintaining skin integrity is imperative to protect from stress caused by massive weight loss and it can help improve its appearance even after the damage is done. A clinical study using 1.5% bakuchiol and 1%
vanilla tahitensis extract in a face serum was done on 43 women who applied it twice daily for 56 days. The women were 32-53 years old and presented signs of naturally aged skin. By the end of the trial, the women showed signs of sag reduction, facial remodeling, skin firming, and radiance boosting effects from the serum.12 Just as with retinoic acid, there are new
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