Peptides in cosmetics: categories, evidence and Dulcia

Peptides in skincare: how they work, which have supporting evidence and when to add them to your routine

The four functional categories of peptides have different levels of clinical evidence — and their effectiveness depends more on the delivery system in the formulation than on the concentration on the label. Signal, neurotransmitter-inhibiting, carrier and enzyme-inhibiting peptides work through different mechanisms; Matrixyl, Argireline and GHK-Cu have the strongest supporting evidence. Without the right delivery system, however, even a proven peptide will not reach its target layer of the skin. Peptides are familiar from several areas: from bodybuilding supplements (peptides for muscle growth, injectable forms), through oral collagen peptides for joints and hair, to medical injections and anti-obesity medicines such as semaglutide.
This article focuses exclusively on topical cosmetic peptides in skincare: those we apply directly to the face in creams and serums. Questions about the side effects of peptides in bodybuilding or peptides in tablet form fall outside its scope. We touch only briefly on the oral use of collagen peptides; you can find out more on our collagen ingredient page.

What are peptides and how do they work in skincare?

“Peptides” are not a single substance — they are a range of short chains with different roles.

What are peptides? Short chains of amino acids acting as cellular messages

The short “oligopeptides” used in cosmetics usually contain 3 to 10 amino acids and have a molecular weight of 600 to 1,500 Da (Lupo & Cole, Dermatologic Therapy, 2007; Gorouhi & Maibach, Int J Cosmet Sci, 2009).
In the skin, they act as signalling molecules. They do not enter the dermis to “replenish collagen”, which is a widespread myth. The mechanism is different: a peptide binds to a receptor on the surface of a fibroblast or another type of skin cell and gives it an instruction. Some instructions say “produce more type I collagen”, others “do not activate enzymes that break down existing collagen”, and others “block the release of acetylcholine at the nerve ending of a muscle”. Each category of peptides has its own receptor target and its own message. A peptide must have a stated active motif — a generic “peptide complex” without a specified motif means nothing. It also needs to reach its target cell; that is what the next section covers.

Four categories of peptides: signal, neurotransmitter-inhibiting, carrier and enzyme-inhibiting

The original classification by Lupo & Cole (Dermatologic Therapy, 2007) divided cosmetic peptides into three categories. Later literature, particularly the review by Gorouhi & Maibach (Int J Cosmet Sci, 2009), added a fourth: enzyme-inhibiting peptides. These four categories are now considered the standard.

In actual formulations, these categories are combined; multi-peptide serums are now the norm rather than the exception. The evidence is strongest for the first three categories. The fourth (enzyme-inhibiting peptides) has robust in vitro results, but clinical data on wrinkles and texture are less convincing and focus more on a supporting role in formulations than on a standalone anti-ageing effect.

Penetrating the stratum corneum: why molecules above 500 Da need a delivery system

Peptides are hydrophilic macromolecules. The stratum corneum, a lipophilic barrier 10 to 30 µm thick on the skin's surface, usually allows only molecules up to approximately 500 Da to pass through. A typical oligopeptide has a molecular weight of 600 to 1,500 Da. Without a technical workaround, a peptide simply cannot reach the place where it needs to act (Vrettos et al., Adv Drug Deliv Rev, 2024).
That workaround is a delivery system. Four approaches are used in practice: lipidation (a fatty acid is attached to the peptide; this is why “Matrixyl” is actually Palmitoyl Pentapeptide-4, a pentapeptide with a palmitoyl chain), liposomal encapsulation, peptide carrier systems such as SPACE peptide, and niosomal or ethosomal nanoformulations. The review by Vrettos et al. (2024) concludes that lipidation can increase peptide deposition in the dermis several-fold; the exact value depends on the peptide, modification and vehicle.
The concentration on the label is not the same as bioavailability. A peptide in a carefully designed cream emulsion with lipid carriers or in a liposomal gel often has better real-world effectiveness than a higher concentration in a simple water-based formula.

Levels of evidence: what is well supported and what still needs clinical data

Not all four categories have the same evidence base.

• Signal peptides (Matrixyl, Palmitoyl Pentapeptide-4): controlled clinical studies with in vivo measurements. In an RCT with n = 93, Robinson et al. (2005) showed a reduction in wrinkle depth over 12 weeks across individual endpoints (replica-based measurements and instrumental skin texture measurements) ranging from approximately 13% to 37%; the mechanism is well described in Lintner & Peschard (Int J Cosmet Sci, 2000). Well supported.
• Neurotransmitter-inhibiting peptides (Argireline, Acetyl Hexapeptide-8): the mechanism at the SNARE complex level is rigorously described (Blanes-Mira et al. 2002). Clinical data on expression lines exist, but most pilot studies have small sample sizes and are manufacturer-funded. Moderately strong evidence.
• Carrier peptides (GHK-Cu): the broadest gene expression evidence (Pickart & Margolina 2018, more than 4,000 modulated genes); the review by Pickart & Margolina (2018) cites a clinical study showing a 31.6% reduction in wrinkle volume compared with 21.6% for Matrixyl-3000 (figures reported in the review). Well supported when correctly formulated.
• Enzyme-inhibiting peptides (soya, rice): strong in vitro inhibition of MMP-1 and MMP-2; clinical data are less convincing, with small samples and often no control group. More of a supporting ingredient than a standalone anti-ageing hero.
• PDRN (polydeoxyribonucleotide): strictly speaking, this is not a peptide. It consists of short DNA fragments with a molecular weight of 50 to 1,500 kDa, isolated from salmon gonadal tissue. In cosmetic practice, however, it is discussed alongside peptides because it acts similarly as a cellular signalling molecule through the adenosine A2A receptor (Galeano et al., Wound Repair Regen, 2008). The most convincing clinical evidence is for injectable PDRN in aesthetic medicine; topical formulations have less data, although the evidence has been growing recently. See also the extensive 2025 review of cosmetic oligopeptides (He et al., 2025).

Peptides in Dulcia skincare: PDRN, Argireline and Milk Peptide Complex

Three systems cover three different mechanisms and were developed within different ranges — which explains why they are not interchangeable.

Salmon PDRN peptide serum: regeneration through DNA fragments

PDRN is polydeoxyribonucleotide, a mixture of short DNA fragments with a molecular weight of 50 to 1,500 kDa, isolated from salmon gonadal tissue (most commonly Oncorhynchus mykiss or O. keta). Its mechanism of action is well characterised: PDRN binds to the adenosine A2A receptor on the surface of fibroblasts and endothelial cells, triggering increased VEGF expression, fibroblast proliferation and collagen synthesis, while also suppressing pro-inflammatory cytokines (Galeano et al., Wound Repair Regen, 2008; He et al., 2025 — an extensive 2025 review).
Clinical evidence for PDRN is strongest for injectable formulations. Intradermal PDRN protocols (such as Rejuran) have been used in aesthetic medicine for years, and published data document improvements in skin texture, elasticity and hydration. The evidence base for topical formulations is smaller but growing, particularly over the last three years.
Dulcia combines PDRN in its serum with SNAP-8 (a heptapeptide (7 amino acids) related to the Argireline motif; the “8” in the trade name refers to the targeted SNAP-25 inhibition, not chain length — INCI Acetyl Glutamyl Heptapeptide-3 according to the supplier's technical data sheet), low-molecular-weight hyaluronic acid and the RejuveNAD™ complex.
PDRN provides the regeneration signal, SNAP-8 targets expression lines, hyaluronic acid also acts as a hydrating vehicle, and the NAD precursor supports cellular metabolism.
A brief technical note: PDRN is not formally a peptide. It is a DNA fragment. Lupo & Cole and Gorouhi & Maibach place it alongside peptides in their reviews because it acts similarly as a cellular signalling molecule with a defined receptor. We therefore keep it within the peptide section of this article.

Argireline Amplified: targeted support for expression lines

Acetyl hexapeptide-8, marketed under the name Argireline, is a 6-amino-acid chain that competitively inhibits the SNAP-25 protein in the SNARE complex (the protein machinery that enables acetylcholine release at a muscle's nerve ending). Its target is the same as that of botulinum toxin type A, but the route is different: botulinum toxin enzymatically cleaves SNAP-25, whereas Argireline only occupies it, preventing vesicle docking (Blanes-Mira et al., Int J Cosmet Sci, 2002).
Daily application results in reduced muscle contraction in areas where the peptide has passed through the stratum corneum, typically the forehead, eye area and glabella. In a pilot study with n = 10 women, Blanes-Mira et al. (2002) documented an approximately 30% reduction in forehead wrinkle depth after 30 days of applying a 10% cream twice daily.
Argireline Amplified, which we use in the Exclusive range (Firming Day Cream, Eye Cream, Intensive Night Cream), is a newer formulation with the same active motif, but produced according to green chemistry principles. Concentrations in individual products range from 2 to 5%, in line with the supplier's recommendations for finished topical products and standard Argireline usage levels in topical skincare.
Argireline is not a replacement for botulinum toxin. After injection, botulinum toxin acts directly deep within the muscle; its effect is pronounced and lasts for months. Topical Argireline acts in the superficial dermis; its effect is milder and gradual, and once application stops, the skin gradually returns to its baseline state. These are two different levels of intervention.

MPC Milk Peptide Complex: signalling from whey proteins

Milk Peptide Complex (MPC) is a peptide complex obtained from whey protein (a by-product of dairy processing) through enzymatic hydrolysis without chemical treatment. The complex is Ecocert and COSMOS certified, in keeping with Dulcia's approach to natural formulations.
The mechanism according to the supplier: a mixture of short amino acid chains acts as a signalling molecule for fibroblasts, reactivating the production of type I collagen, hyaluronic acid and fibronectin. Supplier data: in vivo data report an approximately 25% increase in collagen and a 15% reduction in wrinkle depth at a concentration of 2 to 3% with daily application.
We use MPC in Plus - First Aid for Wrinkles (20 ml), working in synergy with glycolic acid, the fermented marine extract Seafill, the sea fennel extract Aroleat Samphira (a non-irritating retinoid analogue), the microbiotic complex Actibiom and olive squalane. It is designed for more mature skin with signs of fatigue and the first more pronounced wrinkles. The product strikes a balance between affordability and active concentration.

How to add peptides to your routine and what to combine them with

Apply peptide serum to cleansed skin, before your cream. It is not photosensitive, so whether you use it in the morning or evening is not essential; what matters more is what you combine it with. Here are the most common peptide combinations and the guidelines for using them:

• Peptides + retinol: yes, but separately. Retinol belongs in your evening routine (it breaks down in light); you can use peptides in the morning. Both have anti-ageing effects, but through different pathways: retinol acts through retinoid receptors in the cell nucleus, peptides through surface signalling pathways. They complement each other well. Find out more in our separate guide to retinol.
• Peptides + vitamin C: this is not a contraindication, but the low pH of ascorbic acid (typically 2.5 to 3.5) can destabilise some peptides. A safer choice is vitamin C in the morning and peptides in the evening.
• Peptides + hyaluronic acid: a safe and common combination; many peptide serums include HA in the formulation (including our PDRN serum).
• Peptides + AHA/BHA exfoliants: after exfoliating with salicylic or glycolic acid, wait 10 to 15 minutes for the skin's pH to return to normal before applying peptide serum.
• Peptides + Centella (CICA): a good pairing for sensitive and irritated skin. Centella soothes, while peptides support regeneration. Find out more in our guide to centella asiatica (CICA). Clinical studies typically measure changes over 4 to 12 weeks (Blanes-Mira et al. 2002 — 30 days; Robinson et al. 2005 — 12 weeks); you may notice changes in texture and hydration after 6 to 8 weeks, with more pronounced changes in wrinkle depth after 12 weeks or more. Peptides are not a one-week active ingredient. They are long-term signalling molecules.

At Dulcia: why we built our portfolio around PDRN, Argireline and MPC

At Dulcia, we take a layered approach to formulating peptide skincare. PDRN in the serum regenerates at cellular level by activating adenosine A2A receptors; Argireline Amplified in the Exclusive range targets expression lines through competitive inhibition of SNAP-25; MPC in the Plus range signals fibroblasts to produce collagen I and hyaluronic acid.
We chose these three systems because they cover three different mechanisms (regenerative, neurotransmitter-related and signalling) and can be combined without the risk of destabilisation.
You can find out more about individual peptides on our ingredient pages: Argireline, MPC Milk Peptide Complex, hydrolysed elastin and collagen.
An ideal peptide product is the Salmon PDRN Peptide Serum; for more affordable signalling support, we recommend Plus — First Aid for Wrinkles.

Frequently asked questions

Can a peptide serum replace Botox (botulinum toxin)?
No. A topical peptide acts in the superficial dermis and its effect is milder, gradual and reversible; injected botulinum toxin acts deep within the muscle, with a more pronounced effect that lasts for months. Argireline and botulinum toxin target the same protein (SNAP-25), but through different mechanisms and in different layers. They represent two different levels of intervention, not competing alternatives. A peptide serum is a suitable part of daily skincare; botulinum toxin is an aesthetic procedure with its own indications.

Can I combine peptides with retinol?
Yes, but separately. Retinol belongs in your evening routine (it breaks down in light); you can use peptides in the morning or use them in separate routines. Both have anti-ageing effects through different pathways: retinol acts through retinoid receptors in the cell nucleus, peptides through surface signalling cascades. They are complementary, not contradictory. For sensitive skin that is new to retinol, morning peptides help ease the impact of “retinol days” and help the barrier recover.

How long do peptides take to work?
Clinical studies typically measure changes over 4 to 12 weeks (Blanes-Mira et al. 2002 - 30 days; Robinson et al. 2005 — 12 weeks). You may notice changes in skin texture and hydration after 6 to 8 weeks of daily application; more pronounced changes in wrinkle depth and elasticity (those measurable through photography) usually appear after 12 weeks or more. Peptides are not a quick-fix active ingredient — they are long-term signalling molecules that gradually change fibroblast activity.

Are peptides safe for sensitive skin?
Generally yes, with two exceptions: an allergy to milk proteins (MPC) and sensitivity to animal-derived ingredients. Otherwise, peptides are among the best-tolerated anti-ageing actives, considerably gentler than retinol or chemical exfoliants (AHA, BHA). In formulations, they are usually combined with hydrating ingredients and soothing extracts. Sensitive skin still always requires a patch test (testing on a small area of skin, such as the inner elbow).

PDRN comes from salmon — is it suitable for vegans?
PDRN is animal-derived (DNA fragments from salmon gonadal tissue), so it is not suitable for a strictly vegan routine. MPC comes from whey, which means it is not vegan (suitable for lacto-vegetarians, but not vegans). Argireline, on the other hand, is a synthetically produced peptide without an animal source and is suitable for vegans. If you are looking for a vegan peptide option from our portfolio, we recommend products from the Exclusive range with Argireline Amplified.

What is PDRN, and why is it discussed alongside peptides when it is DNA?
PDRN, polydeoxyribonucleotide, consists of short DNA fragments with a molecular weight of 50 to 1,500 kDa. Technically, it is not a peptide (an amino acid chain), but an oligonucleotide (a nucleotide chain). It is discussed alongside peptides because it acts similarly as a cellular signalling molecule through the adenosine A2A receptor, with comparable aims (regeneration, collagen support, hydration). This is a simplification of terminology that we openly acknowledge at Dulcia: when we talk about a “salmon peptide serum”, we mean a serum containing DNA fragments that work together with peptide ingredients in a single formulation.

Conclusion

After reading this guide, you know what to ask about when choosing a serum: the specific active motif (Matrixyl, Argireline, GHK-Cu, PDRN) and the delivery system that carries it into the dermis. The concentration on the label comes last. If you are new to peptides and want a daily product with proven results, Plus - First Aid for Wrinkles is an ideal choice. For even more intensive regenerative action, choose the Salmon PDRN Peptide Serum.

Sources

Lupo MP, Cole AL. “Cosmeceutical peptides.” Dermatologic Therapy 2007; 20(5): 343–349. DOI: 10.1111/j.1529-8019.2007.00148.x.

Gorouhi F, Maibach HI. “Role of topical peptides in preventing or treating aged skin.” International Journal of Cosmetic Science 2009; 31(5): 327–345. DOI: 10.1111/j.1468-2494.2009.00490.x.

Robinson LR, Fitzgerald NC, Doughty DG, Dawes NC, Berge CA, Bissett DL. “Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin.” International Journal of Cosmetic Science 2005; 27(3): 155–160. DOI: 10.1111/j.1467-2494.2005.00261.x.

Blanes-Mira C, Clemente J, Jodas G, et al. “A synthetic hexapeptide (Argireline) with antiwrinkle activity.” International Journal of Cosmetic Science 2002; 24(5): 303–310. PMID: 18498523. DOI: 10.1046/j.1467-2494.2002.00153.x.

Pickart L, Margolina A. “Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data.” International Journal of Molecular Sciences 2018; 19(7): 1987. PMCID: PMC6073405. DOI: 10.3390/ijms19071987.

Vrettos NN, Roberts CJ, Zhu Z. “Peptide-containing nanoformulations: Skin barrier penetration and activity contribution.” Advanced Drug Delivery Reviews 2024; 204: 115124. DOI: 10.1016/j.addr.2023.115124.

Galeano M, Bitto A, Altavilla D, et al. “Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse.” Wound Repair and Regeneration 2008; 16(2): 208–217. PMID: 18318807. DOI: 10.1111/j.1524-475X.2008.00361.x.

Lintner K, Peschard O. “Biologically active peptides: from a laboratory bench curiosity to a functional skin care product.” International Journal of Cosmetic Science 2000; 22(3): 207–218. DOI: 10.1046/j.1467-2494.2000.00010.x.

He Q, Liao Y, Wu Y, Zhang H, Long X, Zhang Y. “Bioactive oligopeptides and the application in skin regeneration and rejuvenation.” Journal of Tissue Engineering 2025; 16: 22808000251330974. DOI: 10.1177/22808000251330974.