ACETYL HEXAPEPTIDE-8

The stratum corneum presents a significant barrier to transdermal delivery. TargetCool is a cooling-assisted delivery device developed to enhance skin penetration, with potential synergistic effects when combined with microneedling systems such as the Turtle pin (0.5 mm) and MTS (1.5 mm). This study aimed to evaluate the effect of TargetCool on the permeability of Acetyl Hexapeptide-8-FITC in an ex vivo human skin model, comparing its performance alone and in combination with microneedling devices. Facial skin samples from Korean female donors aged 50 to 70 years were prepared into 2 × 2 cm sections and assigned to 6 groups: control (topical application only), Turtle pin 0.5 mm, MTS 1.5 mm, Turtle pin 0.5 mm plus TargetCool, MTS 1.5 mm plus TargetCool, and TargetCool alone. Samples were cultured for 24 hours in a Transwell system following treatment with Acetyl Hexapeptide-8-FITC, then processed for H&E and DAPI staining. Optical and fluorescence microscopy were used to assess tissue structure, fluorescence intensity, and penetration depth, with quantitative analysis performed using ImageJ. No structural damage was observed in any group. Compared with the control, fluorescence intensity increased by 504% with Turtle pin, 700% with MTS, 1272% with Turtle pin plus TargetCool, 1000% with MTS plus TargetCool, and 492% with TargetCool alone. Penetration depth increased by 19.01%, 33.10%, 36.88%, 47.75%, and 35.86%, respectively. TargetCool, particularly in combination with microneedling, substantially enhanced the skin penetration and depth of Acetyl Hexapeptide-8-FITC in ex vivo human skin without inducing structural damage. These findings support its potential clinical application in improving transdermal delivery for dermatologic and aesthetic treatments.

This study aimed to explore the anti-skin aging efficacy of a novel serum containing acetyl hexapeptide-8, dipeptide diaminobutyroyl benzylamide diacetate, gluconolactone, niacinamide and laminaria extract through one ex-vivo study and two clinical studies. In ex-vivo study, skin samples were exposed to the serum (Formula 1) and its active ingredient combinations (Formula 2). Biomarkers including matrix metalloproteinase-1, elastic fibres and collagen types I, III, IV and XVII content were analyzed to evaluate the efficacy. In clinical study 1 (n = 50), the Formula 1's efficacy in reducing static wrinkles and improving skin quality was examined, while study 2 (n = 42) focused on its efficacy against dynamic wrinkles. Formula 1 significantly increased levels of anti-aging biomarkers including elastic fibres, collagen fibres, etc. Meanwhile, Formula 1 significantly improved static wrinkle appearance within the first week, with mean clinical scoring from 35% to 69% for various types of wrinkles after 12 weeks of use (all p < 0.001). The clinical scoring for dynamic wrinkles improved by 10%-13% (all p < 0.001). Additionally, significant improvements were observed in skin quality, indicated by clinical scoring changes of smoothness (30%), radiance (27%), skin pore (43%), elasticity (33%) and firmness (36%) (all p < 0.001). The serum demonstrates significant anti-aging effects, effectively improving static and dynamic wrinkles and skin quality. cette étude visait à étudier l'efficacité sur la peau d'un nouveau sérum anti‐âge contenant de l'hexapeptide acétyl‐8, du dipeptide diaminobutyroyl benzylamide diacétate, de la gluconolactone, de la niacinamide et de l'extrait de laminaire dans le cadre d'une étude ex‐vivo ainsi que de deux études cliniques. MÉTHODES: dans une étude ex‐vivo, des échantillons de peau ont été exposés au sérum (Formule 1) et à ses associations de principes actifs (Formule 2). Des analyses des biomarqueurs, notamment de la métalloprotéinase‐1 matricielle, des fibres élastiques et des collagènes de type I, III, IV et XVII, ont permis d'évaluer l'efficacité. Dans l'étude clinique 1 (n = 50), l'efficacité de la Formule 1 dans la réduction des rides statiques et l'amélioration de la qualité de la peau a été examinée, alors que l'étude 2 (n = 42) portait sur son efficacité contre les rides dynamiques. RÉSULTATS: la Formule 1 a significativement augmenté les taux de biomarqueurs anti‐âges, y compris les fibres élastiques, les fibres de collagène, etc. Qui plus est, la Formule 1 a significativement amélioré l'aspect des rides statiques au cours de la première semaine, le score clinique moyen étant de 35% à 69% pour différents types de rides après 12 semaines d'utilisation (p < 0,001 pour tous). Le score clinique pour les rides dynamiques s'est amélioré de 10 à 13% (p < 0,001 pour toutes). En outre, des améliorations significatives ont été observées au niveau de la qualité de la peau, indiquées par des changements de notation clinique de la douceur (30%), de l'éclat (27%), des pores cutanés (43%), de l'élasticité (33%) et de la fermeté (36%) (p < 0,001 pour toutes). le sérum a démontré des effets anti‐âges significatifs en améliorant efficacement les rides statiques et dynamiques ainsi que la qualité de la peau.

This study developed a thermostable, high-loading dissolving microneedle (DMN) system for the transdermal delivery of anti-aging ingredients, 3-O-ethyl ascorbic acid (EAC) and acetyl hexapeptide-8 (AH-8). By using a composite matrix of hyaluronic acid (HA) and polyvinyl alcohol (PVA) in a 3:2 ratio and optimizing a two-step vacuum-assisted micromolding process, we successfully addressed key fabrication challenges, reducing drying time to 2 h and eliminating structural defects. A split-needle design further increased drug loading, reaching 40% for EAC and 20% for AH-8. The resulting DMNs showed excellent mechanical properties, skin penetration efficiency, and biocompatibility in human subjects. In vitro permeation studies using Bama miniature pig skin revealed release profiles influenced by drug-polymer interactions. Despite these differences, both compounds achieved higher cumulative transdermal delivery (EAC: 17.25%; AH-8: 11.29%) than their aqueous solutions. In a UV/D-galactose-induced photoaging mouse model, both EAC-DMNs and AH-8-DMNs significantly reduced visible signs of aging, including wrinkles, skin laxity, and erythema. They also improved skin elasticity and hydration, reversed pathological thickening, and restored oxidative balance by increasing SOD activity and lowering MDA levels. This work provides a scalable, biocompatible, and effective DMN platform, supporting its potential for clinical anti-aging applications.

To overcome natural skin barrier, deliver ellagic acid (EA) to the dermis, and promote its anti-ageing efficacy, oligomeric hyaluronic acid (HA) modified EA-loaded liposomes (EA-HA-L) were constructed via self-synthesized different molecular weights of HA linked cholesterol (HA-Chol), and then the effect of HA molecular weight on the skin permeability of EA was explored to clarify the optimal molecular weight of HA with best transdermal delivery effectiveness. Finally, a series of in vitro and in vivo experiments were conducted to survey the transdermal mechanism, skin irritation, antioxidant, anti-photo ageing and antiwrinkle effects of EA-loaded liposomes modified with the optimal molecular weight of HA. The results showed that EA-HA-L had less than 200 nm particle size and high encapsulation efficiency. Among them, 5 kDa of oligomeric HA-modified liposomes (EA-HA5k-L) maximized the skin penetration and retention of EA and promoted the distribution width of EA in the skin far beyond the thickness of the epidermal layer, indicating its good ability to deliver EA to the dermis. EA-HA5k-L displayed uniformly sized nanosphere morphology and slow-release behavior in neutral and acidic environments that simulated skin. The transdermal mechanism of EA-HA5k-L was proven to be related to the loosening of the stratum corneum, reduction of calcium adhesion proteins, and recognition of CD44 receptor. EA-HA5k-L had no irritant effect on the chicken embryo chorioallantoic membrane, with an irritant index close to 0.9% NaCl. EA-HA5k-L not only improved the clearance rate of EA on DPPH and hydroxyl radicals but also elevated its inhibition effect on elastase. Significantly, compared to free EA and EA-loaded liposomes without oligomeric HA modification (EA-L), EA-HA5k-L significantly increased the cellular uptake of EA through receptor-mediated endocytosis, and effectively blocked the increase in metalloproteinase-1 (MMP-1) content and decrease in type I collagen content induced by UVB in human dermal fibroblasts (HDFs), demonstrating better anti-photo ageing effectiveness. Moreover, EA-HA5k-L upregulated the relative expression of the elastin gene and three types of type I collagen gene (col1a1a, col1a1b, and col1a2) in zebrafish, and its expression promotion rates in col1a1b, col1a2 and elastin were remarkably higher than those of free EA, EA-L, and acetyl hexapeptide-8 as positive control. Conclusively, EA-HA5k-L ameliorated the anti-ageing effectiveness of EA due to the successful transdermal delivery and efficient cellular uptake, and 5 kDa of oligomeric HA-modified liposomes may be a promising transdermal delivery carrier to overcome skin barrier and upgrade the application prospects of EA in anti-skin ageing.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of Acetyl Hexapeptide-8 Amide (synonymous with Acetyl Hexapeptide-8 (sans "Amide")) in cosmetic products; this ingredient is reported to function as a skin conditioning agent - miscellaneous in cosmetics. The Panel reviewed data relevant to the safety of this ingredient in cosmetic formulations, and concluded that Acetyl Hexapeptide-8 Amide is safe in cosmetics in the present practices of use at concentrations up to 0.005%. The Panel further concluded that the available data are insufficient to make a determination that Acetyl Hexapeptide-8 Amide is safe under the intended conditions of use in cosmetic formulations at concentrations greater than 0.005%.

This work developed a dual-function supramolecular co-assembly system based on malic acid-derived ionic liquid (BMa) and acetyl hexapeptide-8 (AHP-8) for enhanced anti-aging transdermal delivery. The system alleviates dynamic wrinkles by inhibiting neurotransmitter release and repairs static wrinkles by promoting collagen production. In vitro transdermal studies showed that the 24-h cumulative permeation of AHP-8 in BMa/AHP-8 was 3.10 times that of free AHP-8. Molecular dynamics simulations revealed that BMa reduces the free energy barrier for AHP-8 permeation mainly due to the interactions between cations and the lipid matrix. Cellular assays demonstrated that BMa/AHP-8 significantly increased collagen I production by regulating the TGF-β pathway and inhibited acetylcholine release more effectively than AHP-8 alone. Clinical trials indicated that the subjects using the BMa/AHP-8 facial cream experienced a greater reduction in wrinkle number, length, and area after 28 days than those using AHP-8 monotherapy. This research provides a novel transdermal delivery approach for developing non-invasive, highly effective anti-aging cosmetic formulations.

Biomimetic peptides represent a growing class of active ingredients in modern cosmeceuticals, designed to mimic the function of the naturally occurring peptides involved in skin homeostasis, repair, and regeneration. Among them, acetyl hexapeptide-8 (AH-8), often referred to as a "botox-like" peptide, has received considerable attention for its potential to dynamically reduce wrinkles through the modulation of neuromuscular activity. AH-8 is widely used in topical formulations intended for anti-aging effects, scar treatment, and skin rejuvenation. This review provides a comprehensive overview of the structure and proposed mechanisms of action of AH-8, with particular focus on its efficacy and skin penetration properties. Due to its hydrophilic nature and relatively large molecular size, AH-8 faces limited permeability through the lipophilic stratum corneum, making effective dermal delivery challenging. Formulation strategies such as oil-in-water (O/W) and multiple water-in-oil-in-water (W/O/W) emulsions have been explored to enhance its delivery, but the ability of AH-8 to reach neuromuscular junctions remains uncertain. Preclinical and clinical studies indicate that AH-8 may reduce wrinkle depth, improve skin elasticity, and enhance hydration. However, the precise biological mechanisms underlying these effects-particularly the peptide's ability to inhibit muscle contraction when applied topically-remain incompletely understood. In some studies, AH-8 has also shown beneficial effects in scar remodeling and sebum regulation. Despite promising cosmetic outcomes, AH-8's low skin penetration limits its bioavailability and therapeutic potential. This review emphasizes the need for further research on formulation science and delivery systems, which are essential for optimizing the effectiveness of peptide-based cosmeceuticals and validating their use as non-invasive alternatives to injectable treatments.

The growing demand for safe and sustainable cosmetics has led to a marked inclination toward natural extracts and peptides as raw materials. In this study, we developed a sustainable system with multiple antiaging effects by combining peony extract (PE) and acetyl hexapeptide-8 (AHP8) to simultaneously treat static and dynamic wrinkles, as well as skin dullness. As the poor skin permeability of AHP8 limited its efficacy, we used a bioactive ionic liquid derived from betaine and malic acid (MA) ([Bet][MA]) as a permeation enhancer. In vitro and in vivo zebrafish experiments indicated that [Bet][MA] not only significantly enhances transdermal and cellular penetration, but also exerts synergistic anti-aging effects. While being biosafe, [Bet][MA] significantly increased the transdermal permeation, skin retention, and cellular uptake of AHP8. Theoretical calculations revealed that [Bet][MA] improved the anti-wrinkle and whitening efficacies of AHP8 and PE through supramolecular interactions; it modulated their electron cloud distribution and molecular polarity and thus intensified their affinity to target proteins. The supramolecular PE/AHP8/[Bet][MA] system demonstrated excellent radical- and reactive oxygen species-scavenging capability, collagen production, and tissue repair capability while concurrently inhibiting tyrosinase activity, motion signaling, and inflammation. The study findings pave the way for sustainable and multifunctional skincare solutions.

Bakuchiol (BAK) and acetyl hexapeptide-8 have favorable biological activities and have promising applications in the cosmetic industry. However, the evaluation of the biological activity of both alone or in combination has not been reported. The biological activity of both alone or in combination was evaluated based on the zebrafish model. Zebrafish embryos were induced to form models using different methods. Add BAK and Argireline YOUth peptide oil solution MB (ARG, containing 0.125% acetyl hexapeptide-8) to treat zebrafish embryos, and they were evaluated for their restorative effects on preexisting damage in zebrafish embryos. BAK and ARG were able to reduce water loss from the caudal fin of zebrafish induced by 0.9% NaCl solution. They were able to alleviate the UVB-induced decrease in the expression level of the skin tightness-related gene (ELN/COL1a1b) in zebrafish embryos, and BAK or ARG effectively reversed the increase in β-galactosidase activity induced by exposure to H 2 O 2 solution and restored telomerase activity in zebrafish embryos. In addition, both were able to counteract oxidative stress and mitochondrial damage in zebrafish embryos as a result of LPS treatment. Finally, BAK and ARG were also effective in suppressing the increase in neutrophil counts and inflammatory cytokine levels in zebrafish embryos due to LPS exposure. Notably, BAK and ARG were more effective when used in combination. Acetyl hexapeptide-8 promotes the bioactivity of BAK in zebrafish embryos (Danio rerio). BAK and ARG have moisturizing, anti-inflammatory, antioxidant, and antioxidant bioactivities in the zebrafish model.

We evaluated real-life experiences of a topical neuro-peptide serum containing 2% acetyl hexapeptide-8, 2% dipeptide diaminobutyroyl, 5% polyhydroxy acids (PHA), 5% niacinamide, and 1% laminaria extract (topical neuro-peptide serum [TNP-serum]). The TNP-serum works synergistically by stimulating 9 key skin biomarkers to reduce wrinkles and produce a skin-brightening effect. Here, we highlight the real-life experiences of 5 dermatologists and 2 surgeons, using an integrated skincare regimen consisting of botulinum toxin type-A (BTX-A) injection in conjunction with twice daily TNP-serum. Real-world cases provide evidence for combination treatments that may be used in cosmetic dermatology to improve patient outcomes and satisfaction. TNP-serum appears to complement BTX-A injections to improve radiance, reduce fine lines, and reduce wrinkles in diverse patients. Incorporating TNP-serum into integrated skincare regimens may offer an additive effect to BTX-A injections and, ultimately, optimize patient results. J Drugs Dermatol. 2024;23:11(Suppl 2):s3-14.

Peptides are increasingly recognized as important therapeutics due to their specificity and potency. However, their clinical application is often hindered by numerous barriers, including low bioavailability, poor cell membrane and tissue penetration. To address these limitations, we developed a library of fluorous penetrating peptides and identified fluorinated hexa-arginine (FR6) as a super-enhancer for cell and tissue penetration. FR6 markedly enhances the intracellular delivery of a variety of peptides by improving membrane permeability, facilitating their uptake across diverse cell types. It greatly improves the penetration of bioactive peptides in 3D tumor spheroids, allowing for improved therapeutic efficacy. More importantly, FR6 demonstrates remarkable potential for transdermal delivery of peptide drugs, effectively enhancing the penetration of peptides like acetyl hexapeptide-8 for treating UVB-induced skin photoaging. Our findings underscore the use of FR6 as a super-enhancer in overcoming multiple physiological barriers during cell, tissue and transdermal delivery.