Application of Acetyl Hexapeptide-8 in Cosmetics: A Review of Skin Permeability and Efficacy
Publish Time:
2025-11-26
In recent years, there has been a surge of interest in peptides as therapeutic agents—particularly biomimetic peptides, which mimic the functions of physiological molecules such as parent proteins and peptides. Bioactive peptides are derived from plants, animals, microorganisms, and synthetic sources. Moreover, they can be rapidly and efficiently synthesized in large quantities in the laboratory. Their physiological functions are diverse, encompassing hormonal activity, immune modulation, as well as antimicrobial, antiviral, and anticancer properties. Due to their growing diversity, selectivity, efficacy, safety, and tolerability, peptides have become a focal point of research and application in the cosmetics industry. The cosmetics industry continues to introduce new peptides, thereby expanding the scope of their use.
Mechanism of action:
Acetyl Hexapeptide-8 (AH-8) is a biomimetic peptide that mimics some of the effects of botulinum toxin. Its primary theoretical mechanism involves competitively inhibiting the binding of SNAP-25 protein to VAMP, thereby disrupting the formation of the SNARE complex and ultimately suppressing acetylcholine release, reducing signal transmission at the neuromuscular junction, and relaxing muscles. In vitro models—such as co-cultures and nematodes—have shown that AH-8 can partially inhibit muscle contraction (e.g., by 26% at 100 ppm). Skin penetration (a key challenge): Some studies indicate that AH-8 can penetrate the stratum corneum from O/W emulsions (with a transdermal penetration rate of approximately 30%) and have observed anti-wrinkle effects. However, other studies suggest that the vast majority of AH-8 (AH-8) remains on the skin surface or is washed off, with only a very small fraction (0.22%) penetrating into the stratum corneum—and no detectable penetration through the full thickness of the skin into the underlying interstitial fluid has been reported. Molecular characteristics pose limitations: AH-8 is highly hydrophilic and has a relatively large molecular weight, making it difficult for it to effectively penetrate the lipid-rich stratum corneum barrier of the skin.
Skin permeability (core challenge):
Some studies have shown that Acetyl Hexapeptide-8 (AH-8) can penetrate the stratum corneum from O/W emulsions (with a transdermal penetration rate of up to 30%) and exhibit anti-wrinkle effects. Other studies (e.g., Kraeling et al.) found that most of the AH-8 remains on the skin surface or is washed off, with only a very small fraction (0.22%) penetrating into the stratum corneum—and no evidence was detected indicating that it could penetrate through the entire skin layer to reach the underlying interstitial fluid. Molecular characteristics pose a limitation: Acetyl Hexapeptide-8 (AH-8) is highly hydrophilic and has a relatively large molecular weight, making it difficult for it to effectively penetrate the lipophilic barrier of the skin's stratum corneum.
The impact of formulation strategies:
Emulsion types: O/W and multiple W/O/W emulsions can promote the skin penetration of AH-8 more effectively than W/O emulsions. Under certain conditions, multiple W/O/W emulsions show potential for outperforming simple O/W emulsions.
pH Value: AH-8 exhibits significantly better solubility and permeability in acidic environments (pH 2.7) than in alkaline environments (pH 7.4), which provides valuable guidance for formulation pH adjustment.
Enhanced Delivery Technology: Microneedle pretreatment can significantly improve the transdermal delivery efficiency of hydrophilic peptides—including Acetyl Hexapeptide-3—providing an effective approach to overcoming the skin's permeability barrier.
Clinical efficacy observation:
Anti-wrinkle: Several in vivo studies have reported that formulations containing 10% acetyl hexapeptide-8 (AH-8) can reduce wrinkle depth by 30% to 49% and improve skin appearance. However, these effects may not be entirely attributable to neuromuscular inhibition. Improvements in parameters such as skin elasticity and hydration varied; some studies did not show significant changes.
Scar Improvement: Clinical studies have shown that topical application of a gel containing Acetyl Hexapeptide-8 (AH-8) can improve the appearance of scars resulting from surgeries and other procedures, as evidenced by increased skin elasticity, reduced sebum secretion, and observed improvements in side effects such as wrinkles and under-eye bags.
Acne and Sebum Regulation: Based on its mechanism of inhibiting acetylcholine release—similar to the cholinergic inhibition of sebaceous glands by BoNT-A—AH-8 is believed to have the potential to reduce sebum production, which could be beneficial for oily skin and as an adjunct treatment for acne. However, further robust direct clinical evidence is still needed in this regard.
A Reconsideration of the Mechanism of Action:
Given the limited transdermal permeability, the observed effects—such as anti-wrinkle and scar-improving benefits—may stem from other mechanisms in the epidermis or the upper layers of the dermis, rather than from direct muscle paralysis. These mechanisms could include local actions such as stimulation of fibroblasts (promoting collagen synthesis), enhancement of skin barrier function, and anti-inflammatory effects.
Implications for cosmetic R&D personnel:
Facing the Challenge of Penetration: When developing products containing peptides—especially hydrophilic macromolecular peptides—it is essential to prioritize and evaluate the skin penetration and bioavailability of the active ingredients. It is not sufficient to simply assume that laboratory efficacy can be directly translated into in vivo effects.
The recipe is key:
Carefully designed delivery systems are crucial. O/W and multiple W/O/W emulsions represent promising avenues for exploration.
Pay attention to the pH value of the formulation and optimize it to promote the stability and permeability of the active ingredients.
Consider using penetration enhancers or other carrier technologies (such as liposomes and nanoparticles) to improve the delivery efficiency of peptides.
Expanding Application Areas: The AH-8 has shown potential value in scar management and sebum regulation; researchers can explore its applications in reparative and oil-control skincare products.
Leverage advanced technologies: Consider combining physical enhancement penetration techniques such as microneedles with peptide-containing products, or develop “device + cosmetic” combination solutions that require professional application, to overcome transdermal barriers.
Various factors influence the ability of a substance to penetrate the skin: the physicochemical properties of the substance; the type of emulsion; the integrity, thickness, and composition of the skin; skin metabolism; the site, area, and duration of application; transdermal delivery characteristics; and the formation of local reservoirs at the application site.
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