AHK-Cu (short for alanine-histidine-lysine bound to a copper ion) is a tiny peptide that carries copper into skin and hair tissue. It belongs to the same family as GHK-Cu, the copper peptide found in many anti-aging creams and wound-care products, but AHK-Cu itself has been tested far less. The one real study on AHK-Cu found that it made human hair follicles grow longer in a lab dish and helped the cells at the base of the hair root survive and multiply. Almost everything else you'll read online about copper peptides and skin or hair health actually comes from research on GHK-Cu, a related but different molecule, and that evidence doesn't automatically carry over to AHK-Cu.
How strong is the evidence?
The direct proof behind AHK-Cu is thin: one lab study that treated isolated human hair follicles and scalp cells in a dish. There is no animal study and no human clinical trial of AHK-Cu on its own. Most of the 34 papers turned up by searching 'copper peptide' or 'copper tripeptide' are actually about GHK-Cu (a different but chemically similar copper peptide) or about copper-peptide chemistry in general. GHK-Cu has real human studies behind it, including one large scalp-injection study, but always as part of a multi-ingredient product, and its results don't prove anything about AHK-Cu specifically. Bottom line: treat AHK-Cu as an early, promising lab finding, not a proven ingredient.
Uses
What people use it for
Supporting hair growth and thicker-looking hair
Animal / labMost interest in AHK-Cu comes from a single lab study showing it made isolated hair follicles grow longer and helped hair-root cells survive and divide. Because of this, it's increasingly added to hair serums and scalp injectable formulas, usually alongside several other active ingredients rather than on its own.
General skin-aging and wound-healing claims (borrowed from its cousin, GHK-Cu)
TheoryBecause AHK-Cu is chemically similar to GHK-Cu, some products market it for wrinkles, wound healing, and firmer skin. Those benefits are documented in some studies of GHK-Cu, not of AHK-Cu itself, so they're an assumption, not a proven fact about AHK-Cu.
Potential benefits
What it may help with
Made hair follicles grow longer and boosted hair-root cell growth, in a lab study
Animal / labIn the only study done on AHK-Cu itself, researchers applied it directly to human hair follicles removed during surgery and to cultured dermal papilla cells (the specialized cells at the hair root that control growth). AHK-Cu made the follicles grow measurably longer and helped these root cells multiply. The researchers also saw fewer of these cells dying off, but that particular difference was small enough that it could have been chance - it wasn't statistically significant. Some internal cell-survival signals did shift in a favorable direction. This is real, but it's a lab dish result, not a study on people using a product.
Studies:17703734Possible skin repair and collagen support - based on the related peptide GHK-Cu, with mixed results
TheoryGHK-Cu, AHK-Cu's close chemical cousin, has been studied for skin repair. After laser skin resurfacing, patients using a GHK-Cu product said their skin looked better, though objective measurements of wrinkles and redness weren't significantly different from a control group. In lab studies, GHK-Cu sped up growth-factor production in skin cells and boosted elastin (a stretch protein in skin). But in an animal wound-healing study, GHK-Cu gel showed no real improvement in blood flow or healing markers compared to plain ointment. None of this evidence is from AHK-Cu directly - it's borrowed from a similar molecule with a mixed track record.
Reduced hair fall and higher hair counts in real-world scalp treatments (as one ingredient among many)
Some human dataSeveral human studies of scalp injections that include copper tripeptide-1 (part of the same chemical family) alongside growth factors, minoxidil, or finasteride reported less hair fall and higher hair counts after months of use. A separate study of a leave-on scalp serum containing copper tripeptide-1 (plus witch hazel, hyaluronic acid, and pea protein) was actually aimed at treating dandruff and a flaky, irritated scalp - its main measured result was less flaking, but it also noted modest gains in hair thickness and density as a secondary finding. These are real people, real results - but because copper tripeptide was always mixed with other active ingredients, there's no way to know how much of the benefit, if any, came from the copper peptide itself.
Improved scar appearance and skin texture in a combination gel
Some human dataA small real-world study of a scar gel containing copper tripeptide-1 plus other ingredients (L-carnitine, hesperidin, hyaluronic acid) found meaningful improvement in scar appearance and skin smoothness over 45 days. Again, this is about a multi-ingredient product, and the copper peptide's individual contribution is unclear.
Studies:41001334
What to watch for
Side effects & risks
- Mild
Mild injection-site reactions (in combination treatments)
In a very large real-world study of a combined hair-loss treatment (oral and topical medication plus a monthly scalp injection that included copper tripeptide among other ingredients), about 4% of patients had minor issues - slight pain, some bleeding, swelling, dizziness, itching, or scalp redness. All resolved on their own, and no serious treatment-related problems were reported. This can't be blamed on the copper peptide specifically, since it was one ingredient in a mixed injection.
- Mild
Copper-bound peptide form appears gentler on skin than raw copper salts
A lab study using skin cells found that GHK-Cu (the related copper peptide) did not trigger irritation markers, while plain copper chloride or copper acetate at the same concentration did. This is reassuring for the copper-peptide format in general, but it was tested on cells in a dish, using GHK-Cu, not AHK-Cu, so it isn't direct proof of AHK-Cu's safety.
Dosing
Dosing — what studies used
There is no established real-world dose for AHK-Cu. No study has tested it as a standalone product on real scalp or skin, in a cream, serum, or injection. The only direct evidence comes from a lab experiment where AHK-Cu was applied to donor human hair follicles and scalp cells at extremely low concentrations (roughly one-trillionth to one-billionth of a mole per liter). That's a lab concentration used to study biology, not a dose you can replicate at home or compare to a skincare product's label. If you see AHK-Cu listed in a commercial product, there is currently no clinical dosing standard to judge it against.
Do not confuse AHK-Cu with GHK-Cu. They are different tripeptides (alanine-histidine-lysine vs. glycine-histidine-lysine, both bound to copper) from the same chemical family. Most published dosing information for 'copper tripeptide' or 'copper peptide' products actually refers to GHK-Cu, not AHK-Cu.
These figures describe what researchers used in studies. They are not a recommendation or a prescription.
Mechanism
How it works
Copper is a mineral your skin and hair cells need to build collagen and elastin (the proteins that keep skin firm and elastic) and to run certain repair enzymes. AHK-Cu is a tiny 3-amino-acid chain that grabs onto a copper ion and can carry it into tissue. In the one real AHK-Cu study, this seemed to help the cells at the root of the hair follicle survive longer and divide more often, which lengthened the hair's active growing phase. Its cousin peptide, GHK-Cu, is thought to work in a similar way - by turning up the skin's natural wound-repair signals and soaking up cell-damaging molecules. Whether AHK-Cu works through the exact same steps inside real human skin is an assumption carried over from GHK-Cu, not something that's been directly proven.
Who should avoid it
- Anyone with a known copper allergy or sensitivity
- People with Wilson's disease or other copper-overload conditions should avoid adding extra copper products
- Pregnant or breastfeeding women - no safety data exists at all
- Anyone expecting drug-level proof of effectiveness - AHK-Cu is not an approved medicine and hasn't been tested in a real clinical trial
Interactions to know
- No drug-interaction studies exist for AHK-Cu.
- In every study that showed a benefit, it was combined with other active ingredients (growth factors, minoxidil, finasteride, hyaluronic acid, or other actives), so its effect used alone is unknown.
The papers that matter most
Key studies
The only study on AHK-Cu itself: it made isolated human hair follicles grow longer and helped the hair-root cells multiply and survive longer in a dish.
The effect of tripeptide-copper complex on human hair growth in vitro
After laser skin resurfacing, patients using a GHK-Cu product reported better skin quality, but objective measures of wrinkles and redness weren't significantly different from controls.
Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin
A large real-world study of scalp injections containing copper tripeptide-1 plus several growth factors found less hair fall and higher hair counts after a year, but the copper peptide's individual contribution can't be isolated.
Intradermal injections of a hair growth factor formulation for enhancement of human hair regrowth
GHK-Cu sped up growth and healing-signal production in human skin cells from radiation-damaged tissue, pointing to a wound-repair mechanism shared by copper peptides.
Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts
In irradiated rat skin flaps, topical GHK-Cu gel showed no significant improvement in blood flow or healing markers versus plain ointment - a reminder that copper-peptide results aren't uniformly positive.
Effects of topical copper tripeptide complex on wound healing in an irradiated rat model
A large combination hair-loss treatment that included an injectable with copper tripeptide among other ingredients was generally well tolerated, with only minor, short-lived side effects like injection-site pain and swelling.
Androgenetic Alopecia Treatment in Asian Men
Bottom line
AHK-Cu has one genuinely promising lab signal for hair-follicle growth, but it hasn't been tested in animals or in a real human trial on its own - treat it as an early-stage lab finding, not a proven treatment, and don't assume it works the same way as its better-studied cousin, GHK-Cu.
Research papers
Studies we have on file for AHK-Cu. Tap a title to open it on PubMed. Labels like “animal” or “human trial” are rough guides.
34 papers
Microneedle-Mediated Delivery of Copper Peptide Through Skin.
Copper peptide (GHK-Cu) plays an important role in skin regeneration and wound healing. However, its skin absorption remains challenging due to its hydrophilicity. Here we use polymeric microneedle array to pre-treat skin to enhance GHK-Cu skin penetration. Two in vitro skin models were used to assess the capability of microneedles in facilitating skin delivery of GHK-Cu. Histological assay and confocal laser scanning microscopy were performed to characterize and quantify the microconduits created by the microneedles inside skin. Cellular and porcine models were used to evaluate the safety of microneedle-assisted copper peptide delivery. The depth and percentage of microneedle penetration were correlated with application forces, which in turn influenced the extent of enhancement in the skin permeability of GHK-Cu. In 9 h, 134 ± 12 nanomoles of peptide and 705 ± 84 nanomoles of copper permeated though the microneedle treated human skin, while almost no peptide or copper permeated through intact human skin. No obvious signs of skin irritation were observed with the use of GHK-Cu after microneedle pretreatment. It is effective and safe to enhance the skin permeation of GHK-Cu by using microneedles. This approach may be useful to deliver similar peptides or minerals through skin.
Copper-tripeptides (cuzymes) with peroxidase-mimetic activity.
Peroxidases are enzymes that use hydrogen peroxide to oxidize substrates such as 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ATBS). In this study, we showed that copper-tripeptide complexes ("cuzymes") also exhibited peroxidase-like activities. Different cuzymes could be formed by using various tripeptide ligands, such as GGG, GGH or HGG. However, the peroxidase-like activity of cuzymes depends on the sequence of the tripeptide (Cu-GGG > Cu-HGG > Cu-GGH). When ABTS was used as the substrate, the activity of Cu-GGG was 326 ± 1.5 U mg-1 which was 2.5 times higher than that of horseradish peroxidase (HRP). Copper-tripeptide complexes were also used to degrade trypan blue dye. By using 0.2 mM Cu-GGG and 0.2% H2O2, 200 μM trypan blue could be degraded in 15 min at 50 °C. The degradation reaction followed second-order kinetics; the reaction rate was proportional to both H2O2 concentration and the copper-tripeptide concentration, but it was independent of the trypan blue concentration. Because copper-tripeptides catalyzed the oxidation reactions involving H2O2 effectively, they may have potential applications in biochemical assays and environmental remediation.
Liposomes as Carriers of GHK-Cu Tripeptide for Cosmetic Application.
Liposomes are self-assembled spherical systems composed of amphiphilic phospholipids. They can be used as carriers of both hydrophobic and hydrophilic substances, such as the anti-aging and wound-healing copper-binding peptide, GHK-Cu (glycyl-L-histidyl-L-lysine). Anionic (AL) and cationic (CL) hydrogenated lecithin-based liposomes were obtained as GHK-Cu skin delivery systems using the thin-film hydration method combined with freeze-thaw cycles and the extrusion process. The influence of total lipid content, lipid composition and GHK-Cu concentration on the physicochemical properties of liposomes was studied. The lipid bilayer fluidity and the peptide encapsulation efficiency (EE) were also determined. Moreover, in vitro assays of tyrosinase and elastase inhibition were performed. Stable GHK-Cu-loaded liposome systems of small sizes (approx. 100 nm) were obtained. The bilayer fluidity was higher in the case of cationic liposomes. As the best carriers, 25 mg/cm3 CL and AL hydrated with 0.5 mg/cm3 GHK-Cu were selected with EE of 31.7 ± 0.9% and 20.0 ± 2.8%, respectively. The obtained results confirmed that the liposomes can be used as carriers for biomimetic peptides such as copper-binding peptide and that the GHK-Cu did not significantly affect the tyrosinase activity but led to 48.90 ± 2.50% elastase inhibition, thus reducing the rate of elastin degeneration and supporting the structural integrity of the skin.
The effect of tripeptide-copper complex on human hair growth in vitro.
The tripeptide-copper complex, described as a growth factor for various kinds of differentiated cells, stimulates the proliferation of dermal fibroblasts and elevates the production of vascular endothelial growth factor, but decreased the secretion of transforming growth factor-beta1 by dermal fibroblasts. Dermal papilla cells (DPCs) are specialized fibroblasts, which are important in the morphogenesis and growth of hair follicles. In the present study, the effects of L-alanyl-L-histidyl-L-lysine-Cu2+ (AHK-Cu) on human hair growth ex vivo and cultured dermal papilla cells were evaluated. AHK-Cu (10(-12) - 10(-9) M) stimulated the elongation of human hair follicles ex vivo and the proliferation of DPCs in vitro. Annexin V-fluorescein isothiocyanate/propidium iodide labeling and flow cytometric analysis showed that 10(-9) M AHK-Cu reduced the number of apoptotic DPCs, but this decrease was not statistically significant. The ratio of Bcl-2/Bax was elevated, and the levels of the cleaved forms of caspase-3 and PARP were reduced by treatment with 10(-9) M AHK-Cu. The present study proposed that AHK-Cu promotes the growth of human hair follicles, and this stimulatory effect may occur due to stimulation of the proliferation and the preclusion of the apoptosis of DPCs.
Injectable amino-modified poly-L-lactic acid microspheres/hyaluronic acid-based hydrogel composites for soft tissue fillers.
Soft tissue fillers have received much attention for the treatment of skin aging and the restoration of missing or excised soft volumes. However, the development of fillers with both safety and applicability remains a challenge. This study presented a synergistic composite filler comprising aldehyde-modified hyaluronic acid (OHA), hydrazide-modified hyaluronic acid (NHA), amino-modified poly-L-lactic acid microspheres (NPLLA), and antioxidant copper peptide. The hydrogel formed in situ via Schiff base reaction exhibited excellent mechanical properties and immediate filling effect. The amino-modified PLLA microspheres were less likely to agglomerate, avoiding the occurrence of adverse reactions and further enhancing the mechanical properties of the filler. The timed-release platform provided protection for copper peptide stability, scavenged reactive oxygen species during the fibrotic encapsulation phase, and synergistically promoted collagen deposition. In a nude mice skin aging model, hydrogels stimulated collagen production through the TGF-β/Smad signaling pathway with good long-term filler efficacy. Therefore, NPLLA microspheres/hyaluronic acid-based composite hydrogels exhibit great potential as injectable soft tissue fillers.
Androgenetic Alopecia Treatment in Asian Men.
Background: Androgenetic alopecia (AGA) is a common form of hair loss in Asian men. Although AGA is often regarded as a relatively minor dermatological condition, hair loss can impact self-image and is a main cause for anxiety and depression in some men. We have treated patients with AGA for seven years. Objective: The goal of this study was to evaluate the effectiveness of our combination therapy in Asian men with AGA. Participants: Between the years 2011 and 2017, 18,918 male patients were treated in our center. Our combination therapy consists of oral finasteride once daily, oral and topical minoxidil twice daily, and an injectable treatment of lidocaine and an AGA treatment solution comprising minoxidil, arginine, aspartic acid, caffeine, copper tripeptide, lysine, niacin, panthenol, propanediol, propylen glycol, retinyl palmitate, pyridoxine, sodium hyaluronate, and ubiquinone once monthly for more than six months. Measurements: Digital photographs were taken pre- and post-treatment, and patient assessments were recorded after six and 12 months post-treatment. Results: Significant improvement was observed in all patients in the digital photographs. Ninety-six and 80 percent of the patients reported satisfaction with the results of the treatment after six and 12 months post-treatment. Minor complications were observed in 802 (4.2%) patients, characterized by slight pain and bleeding due to injection, swelling, dizziness, itching, and erythema of the scalp. Slight pain was reported in 651 patients (3.4%), and slight bleeding was reported in 56 patients (0.3%). Sexual dysfunctions were uncommon. These minor complications resolved spontaneously. No treatment-related adverse events were observed. Conclusion: A combination of these therapeutic options offers safe and highly efficacious treatment for AGA with minimal complications.
Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin.
To evaluate the role of skin care products that contain a copper tripeptide complex, glycyl-l-histidyl-l-lysine-Cu(2+) (GHK-Cu), in treating carbon dioxide (CO(2)) laser-resurfaced skin. Patients meeting the inclusion criteria underwent circumoral skin resurfacing using a CO(2) laser at standard settings. Patients were then randomized to receive posttreatment skin regimens with or without GHK-Cu. Evaluations for erythema throughout the posttreatment period were performed using computer software and blinded evaluators. In addition, overall improvement in wrinkles and overall improvement in skin appearance 12 weeks after treatment were assessed. Patients completed a validated questionnaire before and 12 weeks after treatment. Thirteen patients completed the study. Computer analysis and blinded evaluators found no statistically significant differences between groups for earlier resolution of erythema. All the patients experienced significant improvement in wrinkles and overall skin quality, but no differences were found between groups. The results of the questionnaire indicated a significant difference in the posttreatment improvement of overall skin quality for patients using GHK-Cu (P = .04). Copper tripeptide complex (GHK-Cu) skin care products placed on CO(2) laser-resurfaced skin offered no significant reduction or resolution of posttreatment erythema. Objective evaluation found no significant improvement in wrinkles or overall skin quality. However, patient satisfaction was significantly higher for those who used GHK-Cu skin care products after CO(2) laser skin resurfacing.
Human skin penetration of a copper tripeptide in vitro as a function of skin layer.
Skin retention and penetration by copper applied as glycyl-L-histidyl-L-lysine cuprate diacetate was evaluated in vitro in order to assess its potential for its transdermal delivery as an anti-inflammatory agent. Flow-through diffusion cells with 1 cm(2) exposure area were used under infinite dose conditions. 0.68% aq. copper tripeptide as permeant was applied on isolated stratum corneum, heat-separated epidermis and dermatomed skin and receptor fluid collected over 48 h in 4 h intervals using inductively coupled plasma mass spectrometry to analyze for copper in tissues and receptor fluid. The permeability coefficient of the compound through dermatomed skin was 2.43 ± 0.51 × 10(-4) cm/h; 136.2 ± 17.5 μg/cm(2) copper permeated 1 cm(2) of that tissue over 48 h, while 97 ± 6.6 μg/cm(2) were retained as depot. Copper as tripeptide was delivered in potentially therapeutically effective amounts for inflammatory disease.
Copper(II)-Tripeptide Complexes as Potential Skin Healing Agents: Synthesis, Characterization, and Wound Repair Ability.
Due to the rising incidence of skin diseases, the World Health Organization has emphasized the need for improved prevention and treatment strategies. The search for new compounds active against skin lesions and pathologies has attracted significant attention. This work reports the synthesis, analytical, spectroscopic, and electrochemical characterization of four copper(II)-tripeptide complexes using Gly-Gly-Ile (GGI), Ala-Ala-Ala (AAA), Phe-Gly-Gly (FGG), and Val-Tyr-Val (VYV) as ligands. Results show that GGI, AAA, and FGG monodeprotonate and coordinate to copper(II) through the aminic N and the adjacent carbonyl O, following a 1:2 metal-to-ligand stoichiometry. VYV doubly deprotonates and forms a 1:1 complex with the tripeptide coordinated through the aminic N atom a deprotonated amidic N and a carbonyl O. Aqueous solution studies confirm that the tripeptide stays coordinated in the major species in solution. Complexes are redox active in the biologically relevant window, with CuVYV presenting the most accessible Cu(III)/Cu(II) transition. The ability to promote wound healing was assessed through a scratch wound healing assay. CuAAA and CuVYV are promising inducers of wound healing by promoting migration in MRC-5 cells. Cytotoxicity assays confirm that the compounds are not cytotoxic at the doses used for wound repair, making CuAAA and CuVYV interesting candidates for further studies.
Effect of Peptides on the Synthesis, Properties and Wound Healing Capacity of Silver Nanoparticles.
The aim of this study is the synthesis of novel peptide-silver nanoparticle conjugates with enhanced wound healing capacity. Peptide-silver nanoparticle conjugates were synthesized using myristoyl tetrapeptide 6 (MT6) or copper tripeptide 1 (CuTP1). Peptide-free silver nanoparticles (AgNP) were synthesized using NaBH4 and sodium citrate and were used as control. The addition of the peptides during or after the synthesis of nanoparticles and its impact on the properties of the synthesized peptide-silver nanoparticle conjugates were assessed. The monitoring of the synthesis of nanoparticles was achieved using ultraviolet-visible spectrophotometry (UV-/Vis). The characteristics and colloidal stability of the nanoparticles (size and ζ-potential distribution, morphology, composition and structure) were monitored using dynamic laser scattering (DLS), transmission electron microscopy (TEM), atomic absorption spectroscopy (AAS) and X-ray diffraction (XRD). The wound healing capacity of the peptide-silver nanoparticle conjugates was assessed using scratch test assay on fibroblasts (NIH/3T3). The results indicated that the addition of the peptides during the synthesis of nanoparticles lead to better yield of the reaction and more effective capping while the size distribution and ζ-potential of the conjugates indicated long-term colloidal stability. The MT6-AgNP conjugate exhibited 71.97 ± 4.35% wound closure, which was about 5.48-fold higher (p < 0.05) than the corresponding free MT6. The CuTP1-AgNP conjugate exhibited 62.37 ± 18.33% wound closure that was better by 2.82 fold (p < 0.05) compared to the corresponding free CuTP1. Both peptides led to the synthesis of silver nanoparticle conjugates with enhanced wound healing capacity compared to the respective free peptide or to the peptide-free AgNP (29.53 ± 4.71% wound closure, p < 0.05). Our findings demonstrated that the synthetized peptide-silver nanoparticle conjugates are promising ingredients for wound care formulation.
An Assessment of the Safety, Efficacy, and Tolerability of a Novel Scalp Treatment Regimen Combining a Hydroxy Acid-Based Scrub and Copper Tripeptide Serum in the Management of Seborrheic Dermatitis in Adults.
Background and objective Scalp dandruff, a prevalent dermatological condition marked by flaking and itching, affects a large segment of the population. Sun exposure, genetics, and dryness, along with winter conditions, indoor heating, and hard water, all contribute to moisture loss and scalp imbalance. This study aimed to evaluate the safety, efficacy, and tolerability of a novel regimen combining a scalp scrub with hydroxy acid derivatives for exfoliation and dandruff removal, and a serum containing copper tripeptide-1, witch hazel (Hamamelis virginiana), hesperidin, hyaluronic acid, and pea protein (Pisum sativum) for hydration and scalp health. Methods This prospective, interventional, open-label, single-center study assessed the safety, efficacy, and in-use tolerability of a scalp scrub and serum regimen for mild to moderate dandruff. Ethical approval was granted by ACEAS - Independent Ethics Committee and all participants provided written consent. The study evaluated changes in Adherent Scalp Flaking Score (ASFS), scalp hydration with the Corneometer® CM 825, hair thickness, hair density, and scalp condition using CASLite Nova. Scalp appearance and treatment usage perception were evaluated on day 1, day 8, and day 15. Statistical analysis was conducted using SPSS Statistics v29.0.1.0 (IBM Corp., Armonk, NY) and Microsoft Excel 2019, with results reported as p-values and 95% confidence intervals (CI). Results As per the ASFS scale for adherent scalp flaking, a significant improvement of 61.24% (p<0.0001) was observed by day 15. Assessments with CASLite Nova showed significant increases in hair density and hair thickness by 12.48% (p<0.0001) and 25.36% (p<0.0001), respectively. Regarding scalp condition, the proportion of individuals with a dry scalp and significant keratin decreased from 65.52% at baseline to 6.9% by day 15. The incidence of dry scalp with fine dandruff also decreased from 6.9% at baseline to 0% by day 15. Conversely, the percentage of individuals with a dry scalp and some keratin increased from 27.59% at baseline to 48.28% by day 15. Also, the proportion of subjects with a normal scalp, characterized by good hair density and thickness, increased from 0% at baseline to 44.83% by day 15. Scalp skin hydration, measured by Corneometer® CM 825, showed a significant improvement of 76.24% (p<0.0001) from baseline to day 15. Overall, there were notable enhancements in scalp appearance, with reductions in itchiness, redness, roughness, and scaliness. All subjects reported satisfaction with the treatment. Conclusions The ThriveCo scalp regimen (scalp scrub + serum) has been demonstrated to be both effective and safe in treating and reducing scalp dandruff in healthy adults. The regimen significantly reduced ASFS by effectively removing visible scalp flakes from day 1 to day 15 with continuous use. Furthermore, the kit improved overall scalp condition, increased skin hydration, and enhanced the scalp's appearance. The components include scalp scrub with hydroxy acid derivatives for exfoliation and dandruff removal, and a serum containing copper tripeptide-1, Hamamelis virginiana, hesperidin, hyaluronic acid, and pea protein (Pisum sativum) for hydration and overall scalp health over the 15-day treatment period. The synergistic effects of this regimen work to clear visible dandruff flakes, reduce adherent scalp flaking, rejuvenate the scalp, and simultaneously strengthen the hair.
Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds.
Copper is an essential mineral and plays important roles in skin growth and activity. Copper delivery through skin can provide beneficial effects but its potential to induce skin irritation reactions is often overlooked. Data on dermal toxicity caused by copper compounds is scant. Some recognized in vitro skin toxicity methods are unsuitable for all metal compounds. Here, we employ a keratinocyte-based model and evaluated the skin irritation potential of copper compounds at cellular, genomic and proteomic levels. We determined cell viability and cytotoxicity by using tetrazolium reduction assay and Lactate Dehydrogenase (LDH) assay, performed real-time PCR and protein quantification to assess the expression of biomarkers after treating cells with copper peptide (GHK-Cu), copper chloride (CuCl2) and copper acetate (Cu(OAc)2). These copper compounds exhibited different irritancy potentials at the same treatment concentrations. GHK-Cu was not cytotoxic and did not induce any significant change in the expression levels of various skin irritation-related biomarkers. IL-1α and IL-8, HSPA1A and FOSL1 were significantly upregulated following 24-h treatment with CuCl2 and Cu(OAc)2 at 58 and 580 μM without concomitant inhibition in cell viability. GHK-Cu has a low potential of inducing skin irritation and therefore provides a safer alternative for the delivery of copper through skin.
Rigid-flexible nanocarriers loaded with active peptides for antioxidant and anti-inflammatory applications in skin.
Peptides are recognized as highly effective and safe bioactive ingredients. However, t their practical application is limited and hampered by harsh conditions for practical drug delivery. Hence, a novel peptide nanocarrier of copper peptide (GHK-Cu) encapsulation developed by liposome technology combined with the classical Chinese concept of rigidity and flexibility. Different polyols were selected as modification ligands for phospholipid bilayers to construct a nano drug-carrying system with high loading rate, good stability and biocompatibility. In vitro, this complex not only significantly retarded the release ability of copper peptides, but also enabled copper peptides to be effectively resistant to enzymatic degradation. Furthermore, cellular experiments showed that this system mainly regulates Nrf2, SIRT1, and PEG2/COX-2-related signaling pathways, thus effectively counteracting cellular inflammation, senescence, and apoptosis from oxidative damage. Interestingly, a green, non-toxic, efficient and convenient antioxidant system was developed for the prevention and deceleration of skin aging.
Copper peptide activated cascade catalysis for glucose regulation and hypoxia reversing in infected diabetic wound healing.
Starvation therapy has emerged as a promising strategy in diabetic wounds treating by regulating glucose level to deplete microbial nutrients without inducing antimicrobial resistance. However, this process consumes large amounts of oxygen, exacerbating wound hypoxia and compromising therapeutic efficacy. In this study, we designed a GOX-loaded hydrogel incorporated with copper peptide (GHK-Cu) to construct a copper peptide-activated cascade catalysis system for concurrent glucose regulation and hypoxia reversing. GOX initiates the cascade by catalyzing glucose oxidation, which reduces local hyperglycemia levels and generates hydrogen peroxide (H2O2). Subsequently, copper ions in GHK-Cu activate the subsequent step by mediating the decomposition of H2O2 through a catalase(CAT)-like reaction, releasing local oxygen to effectively alleviate the hypoxic state of the wound, and its own biological activity can further promote skin repair. The research results show that the Gel@GHK-Cu/GOX hydrogel can efficiently facilitates the decomposition of glucose into oxygen via the cascade reaction. Moreover, this hydrogel has been confirmed to have multiple therapeutic effects, including antibacterial activity, tissue repair promotion, antioxidant capacity, and angiogenesis stimulation. In conclusion, the Gel@GHK-Cu/GOX hydrogel provides an effective approach for chronic diabetic wound therapy. Its multifunctional synergistic mechanism offers novel insights for addressing clinical challenges in refractory diabetic wound healing.
Human skin retention and penetration of a copper tripeptide in vitro as function of skin layer towards anti-inflammatory therapy.
The skin retention and penetration characteristics of copper applied as glycyl-L-histidyl-L-lysine cuprate diacetate were evaluated in vitro in order to assess the potential for its transdermal delivery as anti-inflammatory agent. Flow-through diffusion cells with 1 cm(2) exposure area were used under infinite dose conditions. 0.68% aq. Copper as a tripeptide was applied on isolated stratum corneum, on heat-separated epidermis and on dermatomed skin. Receptor fluid collected over 48 h in 4 h intervals was analyzed by inductively coupled plasma mass spectrometry for copper in tissues and receptor fluid. The permeability coefficient of the compound through dermatomed skin was 2.43 ± 0.51 × 10(-4) cm/h; 136.2 ± 17.5 μg/cm(2) copper permeated 1 cm(2) of that tissue over 48 h, while 82 ± 8.1 μg/cm(2) of copper were retained there as depot. Applied tansdermally as the tripeptide on human skin ex vivo, copper permeated the skin and was also retained in skin tissue in amounts potentially effective for the treatment of inflammatory diseases.
One-Pot Synthesis-Biocompatible Copper-Tripeptide Complex as a Nanocatalytic Medicine to Enhance Chemodynamic Therapy.
Chemodynamic therapy (CDT) is a kind of method utilizing hydroxyl radicals (•OH) generated by Fenton or Fenton-like reactions in situ to kill tumor cells. Copper, a cofactor of many intracellular enzymes, which has good biocompatibility, is a transition metal with extremely high efficiency in the Fenton-like reaction. However, when the intracellular free copper exceeds the threshold, it will bring serious side effects. Hence, we used the chelation between glutathione (GSH) and copper ions to produce a nanocatalytic drug, which was named as Cu-GSSG NPs, to fix free copper. With the aid of hydrogen peroxide (H2O2) in vitro, Cu-GSSG NPs catalyzed it to •OH radicals, which could be confirmed by the electron spin resonance spectrum and the degradation experiment of methylene blue. Based on these results, we further studied the intracellular properties of Cu-GSSG NPs and found that Cu-GSSG NPs could react with the overexpressed H2O2 in tumor cells to produce •OH radicals effectively by the Fenton-like reaction to induce cell death. Therefore, Cu-GSSG NPs could be a kind of potential "green" nanocatalytic drug with good biocompatibility to achieve CDT.
Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts.
To evaluate the effects of copper tripeptide (GHK-Cu) on the growth and autocrine production of basic fibroblast growth factor, transforming growth factor beta1, and vascular endothelial growth factor by normal and irradiated fibroblasts in a serum-free in vitro environment. Primary human dermal fibroblast cell lines were established after explantation from intraoperative specimens obtained from patients who had undergone radiation therapy for head and neck cancer. Normal and irradiated fibroblasts were propagated in serum- and growth factor-free media. Treatment groups were exposed to GHK-Cu (1 x 10(-9) mol/L). We measured cell counts and production of basic fibroblast growth factor, transforming growth factor beta1, and vascular endothelial growth factor. Irradiated fibroblasts survived and replicated in serum-free media. The population-doubling times of normal and irradiated fibroblasts exposed to GHK-Cu were faster than those of nontreated controls. Irradiated fibroblasts treated with GHK-Cu doubled at a rate that approximated that of untreated controls, and produced significantly more basic fibroblast growth factor and vascular endothelial growth factor than untreated controls early after GHK-Cu exposure. Irradiated fibroblasts survive and replicate in serum-free media, establishing this model as ideal for evaluating growth factor production in vitro. Copper tripeptide accelerates the growth of normal and irradiated fibroblasts to the point where treated irradiated fibroblasts approximate the population-doubling time of normal controls. An early increase in basic fibroblast growth factor and vascular endothelial growth factor production by GHK-Cu-treated irradiated fibroblasts may improve wound healing.
Novel Applications of CE-ICP-MS/MS: Monitoring of Antiaging GHK-Cu Cosmetic Component Encapsulation in Liposomes.
The hyphenation of the separation technique with the high-sensitive mass spectrometry detection is one of the driving forces of modern analysis enabling measurements in complex matrices. In particular, capillary electrophoresis coupled to inductively coupled plasma tandem mass spectrometry allows for speciation analysis of selected analytes with a superior resolution. The mild, physiological-friendly conditions of this separation technique offer the unique advantage of analyzing chemical entities in their intact form, which has been successfully exploited in various areas. Herein, we report the pioneering application of such a hyphenated technique in the cosmetic field to investigate the encapsulation of copper tripeptide complex (GHK-Cu) in liposomes. By monitoring copper and phosphorus signals, the formation of liposomes via a simple ethanol injection method was confirmed, and the concentration of GHK-Cu in the liposomes was assessed. The application of coupling of capillary electrophoresis with inductively coupled plasma tandem mass spectrometry (CE-ICP-MS/MS) in cosmetic studies could lead to the development of diverse liposomal formulations with preferential properties and expand their accessibility.
QR678 & QR678 Neo Hair Growth Formulations: A Cellular Toxicity & Animal Efficacy Study.
Current treatment modalities are limited in their approach and success for hair loss. QR 678 & QR 678 Neo are new formulations, consisting of a combination of growth factors and peptides. This study demonstrates safety analysis of QR 678 & QR 678 Neo formulation, using in vitro cytotoxicity assay and in vivo animal efficacy. Factors including vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor-1, keratinocyte growth factor, and copper tripeptide 1 (QR 678) or their biomimetic peptides (QR678 Neo) were suspended in a sterile injectable vehicle. The 3-2,5-diphenyl tetrazolium bromide assay was used to explore the cytotoxic effects of each factor used in the compositions in human keratinocyte cell and human fibroblast cell assays. An in vivo analysis, wherein study animals were given intradermal QR 678 & QR 678 Neo injections, was conducted to assess whether the formulations produce hair growth. Also, hair follicle viability was checked by intradermal injection of the pharmaceutical compositions in secondary alopecia. In both formulations, a positive response was observed with respect to the number of mice exhibiting hair growth at the injection sites. The injections caused retention of hair in a 0.25-cm radius around the injection site. On cytotoxicity study, all the factors were found to be safe in human keratinocyte cell and human fibroblast cell assay. A positive response was demonstrated in animals on treatment with the chemotherapeutic agent. Intradermal injections of QR 678 & QR 678 Neo hair growth factor formulations are a safe and efficacious option for alopecia. Results seem encouraging enough to warrant a trial in humans with secondary alopecia, post cancer chemotherapy.
The effect of copper tripeptide and tretinoin on growth factor production in a serum-free fibroblast model.
To evaluate the effect of copper tripeptide and tretinoin on normal and keloid-producing dermal fibroblasts in a serum-free in vitro model. The cellular response was described in terms of viability and secretion of basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF-beta1). Primary cell lines were established from patient facial skin samples obtained during surgery and plated in serum-free media. At 0 hour, copper tripeptide (1 x 10 (-9) mol/L), tretinoin (1 x 10 (-5) mol/L), or appropriate control vehicle was added. Cell counts and viability were established at 24, 72, and 120 hours. Supernatants were collected at the same intervals and were assessed for bFGF and TGF-beta1 concentrations using the enzyme-linked immunosorbent assay technique. Cell lines showed viability between 86% and 96% (mean, 92%) throughout the experiment. Tretinoin-treated normal fibroblasts secreted more bFGF than did controls at 24 hours (P<.05). Tretinoin-treated keloid-producing fibroblasts secreted more TGF-beta1 than did controls at 120 hours (P<.05). Keloid-producing fibroblasts treated with copper tripeptide secreted less TGF-beta1 than did controls at 24 hours (P<.05); a similar trend was observed in normal fibroblasts. Normal fibroblasts treated with tretinoin produced more bFGF than did controls, and this might partially explain the clinically observed tightening effects of tretinoin. Normal and keloid-producing dermal fibroblasts treated with copper tripeptide secreted less TGF-beta1 than did controls, suggesting a possible clinical use for decreasing excessive scar formation.
Tryptophan and Cysteine Oxidation Products Dominate in α-Lactalbumin-Derived Peptides Analyzed with LC-MSn.
α-Lactalbumin (α-La), a major milk whey protein, is comprised of several amino acids prone to metal-catalyzed oxidation (MCO) typical in processing and during storage of foods. New tools are needed for the detection of characteristic oxidation products especially from tryptophan and cysteine that often remain unrecognized when using the traditional methods of carbonyl formation monitoring. In this study, the oxidative changes in α-La were investigated through tryptic digestion and collection of 3 descriptive peptides fitted into a metal-catalyzed oxidation (Fenton reaction) model. The peptide samples were oxidized at +37 °C for 14 d and explored with liquid chromatography-quadrupole ion trap-mass spectrometer (LC-MSn ). The fractionated α-La peptides were valyl-glycyl-isoleucyl-asparaginyl-tyrosyl-tryptophyl-leucyl-alanyl-histidyl-lysine (VGINYWLAHK), leucyl-aspartyl-glutaminyl-tryptophyl-leucyl-cysteinyl-glutamyl-lysine (LDQWLCEK), and tryptophyl+16 -leucyl-alanyl-histidyl-lysyl-alanyl-leucyl-cysteine (W+16 LAHKALC). Oxidation of several amino acids, such as cysteine, histidine, lysine, and tryptophan was observed. In the peptide LDQWLCEK, cysteine was rapidly trioxidized to sulfonic acid, followed by other amino acid side chains as secondary oxidation sites. Tryptophan oxidation was more pronounced in the peptides W+16 LAHKALC and VGINYWLAHK, and also formation of the harmful N-formylkynurenine was observed. As a conclusion, several stable and promising oxidation markers are proposed for α-La, which could be implemented in the evaluation of quality and safety of dairy protein-containing products.
Effects of topical copper tripeptide complex on wound healing in an irradiated rat model.
To evaluate clinical and immunohistopathological effects of topical glycyl-histidyl-lysine-copper (GHK-Cu) on in vivo irradiated rat wounds. Animal model. Academic institution. After dorsal irradiation and a 28-day recovery period, 2 × 8 cm cranially based dorsal flaps were created in Sprague-Dawley rats. Twice daily GHK-Cu gel (test) or aquaphilic ointment (control) was applied for 10 days. Animals were euthanized, digital images of flaps were taken, and harvested tissues were immunohistochemically stained for a vascular endothelium marker, caveolin-1, and vascular endothelial growth factor (VEGF). Digital image analysis was used for outcome measures. Unpaired t-tests were used for statistical analyses; significance of P < .01 accounted for multiple comparisons. By digital analysis of clinical images, 13 test and 10 control animals showed mean ischemic areas of 5.0 cm(2) (SD = 0.9) for tests and 3.8 cm(2) (SD = 1.1; P = .011) for controls. Whole slide digitized images allowed quantification of caveolin-1-stained blood vessels and VEGF expression in fibroblasts at the interface of healing flaps. Caveolin-1 analyses showed a mean of 209.0 vessels (SD = 111.1) and a mean vessel luminal area of 525.7 um(2) (SD = 191.0) in tests and 207.4 vessels (SD = 109.4; P = .973) and 422.8 um(2) (SD = 109.7; P = .118) in controls. VEGF quantified as the percentage of pixels exceeding a colorimetric threshold, with higher fractions of positive pixels indicating more intense staining, showed a mean intensity score of 0.34 (SD = 0.19) in tests and 0.54 (SD = 0.41; P = .169) in controls. Irradiated dorsal rat flaps treated with topical GHK-Cu gel demonstrated no difference in flap ischemia, blood vessel number or area, or VEGF expression compared to controls.
Using Aldara, copper peptide, and niacinamide for skin care.
The author states that Aldara can be effective in treating actinic keratosis, Bowen's disease, and basal cell carcinomas; copper peptide has been shown to be useful in wound healing; and topical niacinamide may be beneficial in treating acne. The full therapeutic potential of these agents in a skin care and rejuvenation regimen remains to be explored.
Intradermal injections of a hair growth factor formulation for enhancement of human hair regrowth - safety and efficacy evaluation in a first-in-man pilot clinical study.
Research has shown the efficacy of hair growth factors in hair regrowth. We describe the intradermal injections of a recombinant, bioengineered hair formulation, containing growth factors, into the scalp skin, for enhancement of hair regrowth and evaluate its efficacy. The objective of this study was to assess the efficacy and safety of the hair growth factor formulation in reducing hair loss and enhancing hair growth. This was an open-label, prospective, single-arm interventional pilot study in which 1000 patients were given intradermal injections of a hair formulation into the scalp skin. The formulation contains vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor, keratinocyte growth factor, thymosin β4, and copper tripeptide-1 suspended in a sterile injectable vehicle. Intradermal injections of this hair formulation were injected into the scalp once every 3 weeks for a total of eight such sessions. Hair pull test was performed before every session. Videomicroscopic and global images were taken at baseline, fourth session, eighth session, and 2 months after the completion of the eight sessions. Relevant safety assessments through physical examination, questionnaires, and appropriate laboratory examination were conducted throughout the study. Significant reduction in hair fall was seen in 83% of the patients on hair pull test. Videomicroscopic image evaluation showed that most patients had a decrease in the number of vellus hairs, increase in number of terminal hairs, and increase in shaft diameter. Seventy-five percent of the patients believed that the hair injections were aiding the treatment of their hair loss, and it was also beneficial in post-hair transplant patients. At 1 year, a statistically significant increase in total hair count (P = 0.002) continued to be seen. Treatment was well tolerated. Intradermal injections of this hair formulation may be a promising option for treating male as well as female patterns of hair loss.
Intramolecular Charge Transfer-Induced Fluorescent Probe for the Sensitive Detection of Copper Tripeptide.
Donor-acceptor-based fluorescent molecules have garnered considerable attention as excellent tool for trace detection of Cu2+ ions, owing to their tunable photophysical properties and higher sensitivity. Concurrently, these molecules may occasionally display undesired fluorescence quenching due to several factors, thereby diminishing selectivity. To address this concern, this work focuses on developing selective and reversible fluorescent sensors for Cu2+ ions. To pursue this, novel fluorescent probes were designed by incorporating donor moieties like diphenylamine and dimethylamine into an imidazopyridine unit. The probes were synthesized and characterized using conventional techniques. As synthesized probes exhibit strong fluorescence attributed to intramolecular charge transfer, confirmed by density functional theory calculations. The HOMO is localized on amine moiety, while LUMO resides on imidazopyridine segment. Utilizing an electron-rich pyridine acceptor as a selective binding site, both probes exhibit exceptional specificity toward Cu2+ ions over other competing metal ions. The binding of Cu2+ induces the ground-state complex formation, evidenced by the appearance of an isosbestic point in the absorption spectrum. This interaction results in a "turn-off" fluorescence response, disrupting the intramolecular charge transfer process that governs donor-acceptor fluorescence. The fluorometric titration method was employed to assess the sensitivity of probes for Cu2+ ions, which exhibited excellent linearity at lower concentrations, achieving a detection limit at picomolar levels. Moreover, owing to their low toxicity, validated by the MTT assay, the probes were successfully utilized for detecting Cu2+ ions in naturally occurring copper proteins. Consequently, the probe comprising of imidazopyridine unit serves as a viable tool for the detection of Cu2+ ions within intricate biological systems.
Dynamic enzyme-mimetic peptide hydrogel for the treatment of bacterial-infected inflammatory wounds.
Peptide-based hydrogels offer biocompatibility and sequence flexibility for wound healing, yet dynamically regulating therapy within the complex wound microenvironment remains challenging. Inspired by natural silk protein and copper-peptide complexes, we designed an amphiphilic peptide that can self-assemble into active center structures similar to natural enzymes, and further form stable hydrogel networks. After coordination with copper ions, the system demonstrates dynamically regulated dual antioxidase activities: superoxide dismutase (SOD)-like behavior under weakly alkaline conditions and peroxidase (POD)-like activity under acidic conditions. This pH-regulated activity conversion process closely mirrors the pH fluctuations commonly observed in infected and inflamed wound sites, enabling real-time adaptation to local microenvironmental changes. In addition, this enzyme-mimicking hydrogel exhibits efficient reactive oxygen species (ROS) scavenging capability and notable antibacterial performance, effectively promoting wound closure and the formation of skin appendages in a bacterial-infected inflammatory wound model. It also exhibits good mechanical properties, especially in terms of self-healing properties and injectability, showing promising prospects for engineering applications. This versatile hydrogel platform, capable of precisely mimicking and dynamically regulating the activity of key enzymes involved in the wound healing process, offers a promising strategy for modulating the wound microenvironment and promoting a more efficient cascade of healing responses. Meanwhile, this work clarifies the structure-activity relationship between the colloidal self-assembly of amphiphilic peptides and the biochemical interface properties of hydrogels, thereby expanding the theoretical framework for designing and controlling biocatalytic interfacial colloidal materials.
A 1 : 2 copper(II)-tripeptide complex for DNA binding and cleavage agent under physiological conditions.
A 1 : 2 copper-tripeptide complex, [Cu(II)(Boc-His-Gly-His-OMe)(2)](2+), was synthesized and structurally characterized. The absorption band at 577 nm suggests a square-planar geometry around Cu(II). The DNA-binding and DNA-cleavage properties of the Cu(II) complex were investigated. The complex binds to calf thymus DNA (CT DNA) in an intercalative fashion and cleaves plasmid pUC-19 DNA hydrolytically at micromolar concentrations under physiological conditions. The intrinsic binding constant (K(b)=1.2x10(2) M(-1)) for the binding of Cu-tripeptide complex with DNA suggests that this complex is suitable for rapid diffusion on the pharmacological time scale.
DNA- and protein-scission activities of ascorbate in the presence of copper ion and a copper-peptide complex.
L-Ascorbic acid, when combined with either copper(II) ion or a copper(II)-tripeptide complex, extensively cleaved several viral DNAs and proteins under in vitro conditions. Neither ascorbate nor copper tripeptide (Cu2+-diglycyl-L-histidine) alone caused any apparent changes on these molecules. Various transition metal ions and reducing agents were examined under comparable conditions to determine the basic requirements for both DNA degradation and protein scission activities. Copper and iron are the two most effective transition metal ions examined that exhibit these activities in the presence of ascorbate. The addition of catalase, but not superoxide dismutase, can partially inhibit the scission of DNA in vitro, suggesting that H2O2 may be involved in these activities. Among the various reducing agents tested, ascorbate was most effective in causing DNA scission and protein cleavage, corroborating the possible role of H2O2 in the cleavage reactions. One of the products of the reactions of copper/ascorbate is probably the hydroxyl radical generated from H2O2, which can be formed from the oxidation of ascorbate.
Fractional non-ablative laser-assisted drug delivery leads to improvement in male and female pattern hair loss.
Androgenetic alopecia, also known as male and female pattern hair loss, is a very prevalent condition; however, approved therapeutic options are limited. Fractionated laser has been proposed to assist in penetration of topical medications to the cutaneous tissue. We present four cases of androgenetic alopecia that underwent treatment with a non-ablative erbium glass fractional laser followed by the application of topical finasteride 0,05% and growth factors including basic fibroblast growth factor, insulin-like growth factor, vascular endothelial growth factor, and copper peptide 1%. During all laser treatment sessions, eight passes were performed, at 7 mJ, 3-9% of coverage and density of 120 mzt/cm2. A positive response was observed in all of the four patients. Photographs taken 2 weeks after the last session showed improvement in hair regrowth and density. No significant side effects were observed.
Cutaneous Delivery of Cosmeceutical Peptides Enhanced by Picosecond- and Nanosecond-Domain Nd:YAG Lasers with Quick Recovery of the Skin Barrier Function: Comparison with Microsecond-Domain Ablative Lasers.
Picosecond or nanosecond-domain non-ablative lasers generate faster photothermal effects and cause less injury than microsecond lasers. In this study, we investigated the enhancing effect of 1064 nm picosecond- and nanosecond-domain neodymium (Nd):yttrium-aluminum-garnet (YAG) lasers on the cutaneous delivery of cosmeceutical peptides. Microsecond-domain fractional ablative CO2 and fully ablative erbium (Er):YAG lasers were also used for comparison. In the Franz diffusion cell study, pig or mouse skin was treated with a laser before exposure to palmitoyl tripeptide (PT)-1, PT-38, and copper tripeptide (CT)-1 at a concentration of 150 μM. Psoriasiform, atopic dermatitis (AD)-like, and photoaged skins were also developed as permeation barriers. The non-ablative laser elicited the ultrastructural disruption of the stratum corneum and epidermal vacuolation. All laser modalities significantly increased the skin permeation of peptides in vitro. The non-ablative laser chiefly enhanced peptide delivery to the receptor compartment, whereas the ablative laser mainly increased the intracutaneous peptide deposition. The picosecond- and nanosecond-domain Nd:YAG lasers elevated the amount of PT-1 in the receptor up to 40- and 22-fold compared with untreated skin, respectively. Laser treatment promoted peptide delivery in barrier-deficient and inflamed skins, although this enhancement effect was less than that observed in healthy skin. Fluorescence microscopy indicated the capability of the non-ablative laser to deliver peptides to deeper skin strata. The ablative laser confined the peptide distribution in the epidermis. Confocal microscopy showed that peptides penetrated the skin along the microdots created by the fractional Nd:YAG and CO2 lasers. The skin barrier function determined by transepidermal water loss suggested quick recovery when using a nanosecond-domain laser (within 4 h). A longer period was needed for the skin treated with the fully ablative Er:YAG laser (76-84 h). Nanosecond non-ablative laser-facilitated peptide delivery may become an efficient and safe approach for cosmeceutical applications.
Efficacy and Safety Assessment of ThriveCo Scar Fader Gel With Scarcede™ in the Treatment of Skin Scars.
Introduction Skin scars, a natural outcome of dermal injury healing, may seem minor but often lead to significant disfigurement and psychological distress. This study aimed to assess the safety and efficacy of ThriveCo Scar Fader Gel containing Scarcede™ (Anveya Living Private Limited, Bengaluru, India), a proprietary blend of copper tripeptide-1, L-carnitine L-tartrate, alpha-glucosyl hesperidin, and sodium hyaluronate. This synergistic formulation targets multiple scar-improvement mechanisms, offering potential for enhanced skin texture and minimized scar appearance. Method An open-label, interventional, prospective real-world evidence study was conducted to evaluate the clinical safety, efficacy, and in-use tolerability of the test product in females with acne scars. Ethical approval was granted by the Independent Ethics Committee, and informed consent was obtained from all participants. Visible scar changes were assessed using the Manchester Scoring Scale by a dermatologist. Skin texture changes, including smoothness, roughness, and scaliness, were evaluated using VISIOSCAN® VC20 Plus (Courage + Khazaka electronic GmbH, Cologne, Germany). Digital photographs documented progressive scar visibility reduction. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 29.0.1.0 (Released 2022; IBM Corp., Armonk, New York) and Microsoft® Excel 2019 (Microsoft Corporation, Redmond, Washington), with significance reported at the 5% level. Result The test product reduced scar appearance by 7.17% at day 21 (p<0.001) and 26.57% at day 45 (p<0.0001). Skin smoothness improved by 33.08% at day 21 (p<0.0001) and 44.56% at day 45 (p<0.0001). Skin roughness decreased by 100.86% at day 21 (p<0.0001) and 161.62% at day 45 (p<0.0001). Scaliness reduced by 39.71% at day 21 (p<0.001) and 58.92% at day 45 (p<0.0001). No local or systemic adverse effects were reported. Conclusion ThriveCo Scar Fader Gel with Scarcede™ demonstrated clinical safety and efficacy in scar reduction, supporting smoother, clearer skin without adverse effects and suitable for routine skincare use.
Multi-Target Restoration of Dermal Elastic Fibers Through Elastin Upregulation, Elastase Suppression, and Scaffold Reinforcement.
Elastic fibers are key components of the skin extracellular matrix and are essential for maintaining skin integrity and elasticity. During skin aging, particularly photoaging, elastic fiber integrity is progressively compromised by increased elastase activity and the downregulation of elastin and scaffold-related gene expression. Therefore, effective strategies to preserve elastic fiber function should address not only elastin synthesis but also enzymatic degradation and scaffold integrity. In this study, we investigated a multitarget approach to restoring the elastic fiber network by modulating elastin production, elastase activity, and scaffold protein expression. We found that Copper Tripeptide-1 enhanced elastin expression and secretion, ethyl ferulate inhibited elastase activity, and cedrol promoted scaffold-related gene expression and microfibrillar protein restoration in dermal fibroblasts. To assess the biological relevance of this approach, the combined treatment was evaluated using UV-damaged human skin biopsy samples. This combination effectively mitigated UV-induced elastic fiber disruption and significantly improved fiber architecture, as confirmed by immunofluorescence staining and scanning electron microscopy. These findings indicate that coordinated modulation of elastin production, proteolytic protection, and scaffold reinforcement is essential for maintaining elastic fiber integrity and represents a promising approach for preserving skin elasticity during aging.
Complexation of copper ions with histidine-containing tripeptides immobilized on solid surfaces.
Short oligopeptides that complex with metal ions with high affinity and high specificity are of interest to the design of chemical sensors. In this study, we compare the complexation properties of two copper-selective tripeptides, Gly-Gly-His and His-Gly-Gly, either in aqueous solutions or immobilized on solid surfaces. Our results show that the copper complex formed by Gly-Gly-His is more stable than the complex formed by His-Gly-Gly in aqueous solutions, because the position of histidine (His) in the Gly-Gly-His permits the formation of a tetragonal copper complex with a high stability. However, when the tripeptides are immobilized on aldehyde-decorated silicon wafer surfaces under a reaction condition that gives rise to near maximum surface densities of tripeptides, both immobilized Gly-Gly-His and His-Gly-Gly experience strong steric hindrance on the over-crowded surfaces. The surface crowding effect causes less complexation with copper ions than that in aqueous solutions. To ensure a proper surface density on the surface for complexation with copper ions, a so-called two-dimensional (2D) metal-ion imprinting technique is employed to avoid the surface crowdedness. By immobilizing Gly-Gly-His in the presence of copper ions, we create a tripeptide-functionalized surface that exhibits high complexation capability for copper ions. We attribute the higher copper complexation capability to the proper intermolecular distances obtained from the ion-imprinting procedure that gives the copper-tripeptide complex a preferential tetragonal geometry. Our results show that the amounts of copper complexed to a copper-imprinted surface functionalized with Gly-Gly-His are 62% higher than those of a nonimprinted surface.
Impact of single-dose application of TGF-β, copper peptide, stanozolol and ascorbic acid in hydrogel on midline laparatomy wound healing in a diabetic mouse model.
Despite numerous advances and improvements in surgical techniques the incidence of incisional hernias after laparotomy remains high. The aim of this study was to investigate possible effects of single application of ascorbic acid, stanozolol, a synthetic anabolic steroid, copper peptide and transforming growth factor-β (TGF-β) on laparotomy wound healing in an incisional wound model in diabetic mice. After diabetes induction with streptozotozin in Balb-c mice, midline laparatomies were carried out. Closure of the linea alba was followed by single-dose application of the agents dissolved in a hydrogel before skin closure. The functional outcome was assessed in terms of maximum tensile strength. In addition, vessel densities, collagen contents and proliferation, were measured. The breaking strength of the skin 14 days after surgery was significantly higher in ascorbic acid (ΑΑ)-treated incisional wounds, whereas the other agents did not show a significantly better functional outcome. No significant differences were seen in vessel densities. Collagen type III contents was higher in the ΑΑ-treated animals, whereas the percentage of Ki67-positive nuclei was lower compared to the other groups. These data underline the positive effect of topically applied ascorbic acid in wound healing.
Quick links (PubMed)
- PMID 25690343 — 2015 · Microneedle-Mediated Delivery of Copper Peptide Through Skin.
- PMID 35515638 — 2020 · Copper-tripeptides (cuzymes) with peroxidase-mimetic activity.
- PMID 37896245 — 2023 · Liposomes as Carriers of GHK-Cu Tripeptide for Cosmetic Application.
- PMID 17703734 — 2007 · The effect of tripeptide-copper complex on human hair growth in vitro.
- PMID 40876092 — 2026 · Injectable amino-modified poly-L-lactic acid microspheres/hyaluronic aci…
- PMID 30057663 — 2018 · Androgenetic Alopecia Treatment in Asian Men.
- PMID 16847171 — 2006 · Effects of topical copper tripeptide complex on CO2 laser-resurfaced ski…
- PMID 20721598 — 2011 · Human skin penetration of a copper tripeptide in vitro as a function of …
- PMID 42047624 — 2026 · Copper(II)-Tripeptide Complexes as Potential Skin Healing Agents: Synthe…
- PMID 37896231 — 2023 · Effect of Peptides on the Synthesis, Properties and Wound Healing Capaci…
- PMID 39449909 — 2024 · An Assessment of the Safety, Efficacy, and Tolerability of a Novel Scalp…
- PMID 27892491 — 2016 · Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain C…
- PMID 38394858 — 2024 · Rigid-flexible nanocarriers loaded with active peptides for antioxidant …
- PMID 42404628 — 2026 · Copper peptide activated cascade catalysis for glucose regulation and hy…
- PMID 20703511 — 2010 · Human skin retention and penetration of a copper tripeptide in vitro as …
- PMID 33689270 — 2021 · One-Pot Synthesis-Biocompatible Copper-Tripeptide Complex as a Nanocatal…
- PMID 15655171 — 2005 · Effects of copper tripeptide on the growth and expression of growth fact…
- PMID 39451062 — 2024 · Novel Applications of CE-ICP-MS/MS: Monitoring of Antiaging GHK-Cu Cosme…
- PMID 32983753 — 2020 · QR678 & QR678 Neo Hair Growth Formulations: A Cellular Toxicity & Animal…
- PMID 11176716 — 2001 · The effect of copper tripeptide and tretinoin on growth factor productio…
- PMID 28796377 — 2017 · Tryptophan and Cysteine Oxidation Products Dominate in α-Lactalbum…
- PMID 23744835 — 2013 · Effects of topical copper tripeptide complex on wound healing in an irra…
- PMID 19336143 — 2004 · Using Aldara, copper peptide, and niacinamide for skin care.
- PMID 29482481 — 2018 · Intradermal injections of a hair growth factor formulation for enhanceme…
- PMID 40359517 — 2025 · Intramolecular Charge Transfer-Induced Fluorescent Probe for the Sensiti…
- PMID 41785703 — 2026 · Dynamic enzyme-mimetic peptide hydrogel for the treatment of bacterial-i…
- PMID 19479842 — 2009 · A 1 : 2 copper(II)-tripeptide complex for DNA binding and cleavage agent…
- PMID 6654857 — 1983 · DNA- and protein-scission activities of ascorbate in the presence of cop…
- PMID 29452017 — 2018 · Fractional non-ablative laser-assisted drug delivery leads to improvemen…
- PMID 35214181 — 2022 · Cutaneous Delivery of Cosmeceutical Peptides Enhanced by Picosecond- and…
- PMID 41001334 — 2025 · Efficacy and Safety Assessment of ThriveCo Scar Fader Gel With Scarcede&…
- PMID 42193036 — 2026 · Multi-Target Restoration of Dermal Elastic Fibers Through Elastin Upregu…
- PMID 17902718 — 2007 · Complexation of copper ions with histidine-containing tripeptides immobi…
- PMID 22614259 — 2012 · Impact of single-dose application of TGF-β, copper peptide, stanoz…