Skin proteins—keratin, melanin, collagen, elastin, gelatin—give structure to cells, transmit signals from the cell surface to the organelles and mitochondria, and control the regeneration of tissues. Peptides, which are protein fragments, are often used in skincare formulations to activate or change skin cell behavior. “Peptides are short chains of amino acids: A chain of about 50 or fewer amino acids is a peptide; about 50 or more is a protein. This is relevant because certain cells can be signaled to make more of a protein by ‘seeing’ a fragment of that protein,” says John Kulesza, president of dermatologist skincare brand Young Pharmaceuticals.
Formulating peptides is a bit like the game Name That Tune, where the object is to identify a song in as few notes as possible, suggests Kulesza. “The smaller the number of amino acids in the peptide chain, the better its chances of penetration. Of course, to be effective it also has to include enough amino acids to convey a message to the cell,” he notes. “Most peptides used in skincare products are oligopeptides, consisting of 3 to 10 amino acids,” says Jeannette Graf, MD, director of dermatology at Omni Aesthetics MD in New York City. Tripeptides have three amino acids, tetrapeptides have four and so on.
Peptides’ size and lack of reactivity means they fit well into light, elegant emulsions. “They’re great because they can be combined with botanical actives without affecting color or fragrance,” says Debbie Fitzpatrick, VP of sales and marketing at Botanical Science, Inc. “They allow us to enhance effectiveness and keep our products light in weight and high in absorbency,” she adds.
Read on for an overview of peptide formulations and functions—and a peek at new developments in this ever-evolving skincare category.
First-class Formulations – Many peptides have been shown to be effective when tested under lab conditions, but that doesn’t always mean they’ll work in the real world. A product’s effectiveness depends on its ability to deliver enough peptides to the proper skin depth. That’s not the only consideration, however— formulation is complicated by the following:
Level of Actives: Most peptides are created by major ingredient laboratories like Lipotec and Sederma, which also test the peptides to determine effective percentages. “If a product emulsion doesn’t contain the required dosage or percentage, it’s virtually ineffective,” says Liz Cocchia, CEO of Vitelle Lab. “A second issue is consistent application. Peptide products must be applied morning and evening for maximum benefit.”
Combination of Actives: Formulations may need to include several peptides to achieve a specific goal. “Combining peptides can sometimes provide greater results than using just one,” says Cocchia, who offers the examples of hexapeptide-8, hexapeptide-30 and pentapeptide-18, which more effectively decrease wrinkles and expression lines when combined.
Ingredient Penetration: Only peptides smaller than 500 daltons can readily pass through the skin barrier,” explains Neal Kitchen, executive vice president of strategy and development for HydroPeptide. “More problematic is the fact that peptides are naturally hydrophilic (water-based), which means they resist going though the lipophilic (oil-based) barrier layer of the epidermis.” Fortunately, formulators have discovered a number of ways to improve skin penetration. “For example, peptides can be modified with a fatty acid (e.g., palmitoyl or myristoyl), or an acetyl group that significantly improves its ability to penetrate the lipid layer of the skin,” says Kitchen. “A peptide solution should be designed with ingredients that stabilize the solution and help condition the skin for peptide penetration.”
Intended Use: “Peptides tend to be most effective in areas where the skin barrier is thinner, such as under the eyes, and on the neck and chest,” says Kulesza.
To make its way into a skincare formulation, a peptide undergoes a huge amount of testing. “Various concentrations of the peptide must be used to find the most effective level and, most importantly, to find the best way to deliver the peptide formulation into the skin,” says Jeannette Graf, MD, director of dermatology at Omni Aesthetics MD in New York City. Prior to cosmetic use, synthetic peptides are tested extensively for safety. However, what’s currently missing with peptide formulations, as with many skincare products, is evidence of efficacy supported by large, well-designed clinical trials. Because of a current scarcity of such studies, professionals recommending skin care must base their choices on what we know about the basic science behind skincare ingredients and the reputations of the formulators involved. The good news is that there are some exciting formulations coming up the ranks. “On the horizon are biomimetic peptides, which are developed synthetically to specifically fit cell receptor sites,” says Liz Cocchia, CEO of Vitelle Lab. “They’re able to allow the epidermis and dermis to communicate more effectively, which is vital in collagen production.”
Countless possible peptide sequences and combinations mean there’s vast potential for ongoing improvement. “Through the years, there have been several instances where peptide sequences were slightly modified from the original sequence to boost their targeted effects,” points out Kitchen. “Adding palmitoyl to tripeptide-1 (Pal-GHK) improved its skin penetration, and acetyl octapeptide-3 is an elongated version of the Argireline hexapeptide that has been shown to be 30% more effective,” he shares. “Whether it’s next-generation peptides or peptides with new activities, it’s important that we continue to discover innovative ways to utilize these anti-aging tools.”
Peptides are categorized by how they function in the skin. Most fall into one of three categories: Anti-wrinkle peptides. These interfere with the neuromuscular junction to decrease muscle contractions, thereby reducing wrinkles—such as crow’s feet and frown lines—that result from repetitive movements. The most common is Argireline (acetyl hexapeptide-8 or acetyl hexapeptide-3, Lipotec). Short-term clinical trials have shown that 10% Argireline can inhibit the ability of facial muscles to contract. “We use acetyl hexapeptide-3 along with palmitoyl pentapeptide-4 in Botanical Science’s antiaging Luminous Peptide Serum,” says Fitzpatrick. Other neuropeptides include pentapeptide-18 and acetyl hexapeptide-30, both of which work to lessen wrinkle depth, according to Cocchia.
Signaling peptides. These are designed to either stimulate or suppress a specific cell activity. “For example, palmitoyl tripeptide-5 mimics the activity of a protein that activates TGF-ß,” says Kitchen. “Activated TGF-ß stimulates collagen synthesis and suppresses stress-induced collagen degradation.”
Among the best-known signaling peptides are Matrixyl and Matrixyl 3000. “Matrixyl mimics procollagen (the precursor of collagen) and in doing so ‘fools’ the skin into producing more collagen, which results in wrinkle reduction,” says Graf. “It has been tested in many studies using concentrations between 2% and 8%, with 8% being the most effective.”
Matrixyl (palmitoyl pentapeptide) is proprietary to Proctor & Gamble. Used by many formulators, Matrixyl 3000 (palmitoyol pentapeptide-4, Sederma) is similar to Matrixyl but includes additional peptides. Other widely recognized signaling peptides include acetyl hexapeptide-37 (Diff uporine, Lipotec), designed to upregulate aquaporin-3, which moves water from inside the body to the skin; Dermaxyl (Sederma), which stimulates cell communication that repairs age-related skin damage; oligopeptide-68 (ß-White, Lucas Meyer), which inhibits melanin production; and palmitoyl hexapeptide-12 (or palmitoyl oligopeptide), which, says Cocchia, is believed to stimulate collagen production.
These play a key role in delivering nutrients, essential metals, and even other peptides and proteins to the skin. Notes Kitchen, “Copper is an important cofactor in collagen synthesis by down-regulating MMPs (matrix metalloproteinases). The well-known tripeptide GHK helps facilitate copper uptake to the skin.”
–By Linda W. Lewis