Peptides

Peptides are celebrated for their multifaceted roles in skin rejuvenation and repair in the skincare industry. This article explores the mechanisms of action of various peptide classes—including signaling peptides, carrier peptides, neurotransmitter-inhibiting peptides, and enzyme-inhibiting peptides—examines clinical evidence supporting their efficacy, discusses regulatory considerations, and outlines formulation strategies for optimal application.​

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What are Peptides?

Peptides are biological substances which can take many different forms and perform an array of biological functions. They are made up of amino acids joined together by peptide bonds. There are 20 known amino acids, the uniqueness of which is determined by the R group (as displayed in the diagram below).

Amino acids are composed of three main constituents; the carboxylic acid group, amine group and the R group (which varies depending on the amino acid type. The R group variations in singular peptides is what allows for the high diversity of proteins.

A condensation reaction takes place between amino acids to form a peptide (a chain of amino acids). The formation of a peptide with varying amino acids gives rise to an assortment of unique peptides, each with specific properties.

The above diagram illustrates how two amino acids undergo a dehydration reaction (illumination of water, H2O) to form a peptide bond.

The different R groups of these amino acids contain different functional groups. Based on the sequence of amino acids and the chain length, they can provide unique properties when applied topically to the skin. The four major types of peptide ingredients are listed below.

What are the types of peptides in skincare?

Skincare peptides can be divided into four distinguished types based on their functionalities. The four types are: signalling peptides which function as chemical messengers to the skin, carrier peptides which are able to deliver actives into the skin, enzyme inhibiting peptides which inhibit (prevent) the actions of enzymes in the skin, and finally, neurotransmitter inhibiting peptides inhibit (prevent) chemical releases at the neuromuscular junction.

Signalling peptides

When skin is injured, proteases break down damaged tissue into different peptide fragments. These ingredients act as messengers to signal skin to produce different types of tissue to promote healing. Applying these ingredients tricks skin into thinking that it is injured and needs to make additional types of proteins. Signalling peptides typically contain an active amino acid sequence that can induce or inhibit the formation of a specific type of protein. 

Signalling peptides have been developed that claim to stimulate collagen, elastin, laminin, hyaluronic acid, elafin, epidermal growth factor (EGF), thrombospondin I (THBS1), decorin, melanocyte-stimulating hormones (MSH), granulocyte- macrophage colony-stimulating factor (GM-CSF) and fibronectin.

An example of a signalling peptide cosmetic is The Ordinary’s Matrixes 10% + HA

Signalling peptides Examples

Biopeptide-CL Common name: Pal-GHK

Stimulates collagen and glycosaminoglycans synthesis.

Peptamide-6 Common name: FVAPFP

Increases collagen synthesis, upregulates growth factors, transmembrane, matrix and cell shock proteins.

Pal-KTTKS Common name: Matrixyl

Increases collagen synthesis, upregulates growth factors, transmembrane, matrix and cell shock proteins.

Human growth hormone Common name: hGH

Increases collagen synthesis, upregulates growth factors, transmembrane, matrix and cell shock proteins.

Transforming growth factors Common name: TGFα and TGFβ

Reversibly inhibits keratinocytes and leucocytes growth, promotes keratinocyte migration, chemotactic for macrophages and fibroblasts.

Carrier peptides

Carrier ingredients act as facilitators to transport important trace elements (such as copper and manganese) necessary for wound healing and enzymatic processes. These ingredients and proteins are known as penetrating peptides or membrane transduction peptides and have basic transduction domains in their structure.

The main peptide used in transporting copper is the Copper Tripeptide Complex, also known as GHK-Cu. When applied topically to the skin, the peptide functions as an antioxidant, which promotes collagen and elastin production. This mechanism allows for the reduction in fine lines and wrinkles after prolonged use.

An example of a carrier peptide cosmetic is The Ordinary’s “Buffet” + Copper Peptides 1%

Carrier peptides Examples

Copper tripeptide complex Common name: GHK-Cu

Promotes ‘extra-large’ collagen aggregates degradation, more regularly collagen synthesis, elastin, proteoglycans, glycosaminoglycans production and anti-inflammatory and antioxidant responses.

Enzyme-inhibiting peptides

Enzyme-inhibitor peptides act directly or indirectly to inhibit an enzyme. Due to the vast diversity of enzymes, each peptide in this category is unique and serves a distinctive function. Some inhibit the formation of proteinases (enzymes which break down proteins in the skin) and others inhibit lipid peroxidation (the degradation of lipids in the skin).

Enzyme-inhibiting peptides Examples

Soybean protein/amino acids Common name: Preregen

Inhibits the formation of proteinases, increases trichoblast and atrichoblast numbers, increases the number and length of the root hairs.

Silk protein Common name: Sericin

Chelates with copper, inhibits lipid peroxidation and tyrosinase activity and keratinocyte apoptosis.

Rice peptides Common name: Colhinin

Inhibits matrix metalloproteinase activity and induces expression of hyaluronan synthase 2 gene in keratinocytes.

Neurotransmitter-inhibiting peptides

Smiling, frowning, grinning or resting bitch face – your facial muscles are constantly working and moving your skin. Neurotransmitter-inhibiting peptides work to inhibit acetylcholine (a neurotransmitter) release at the neuromuscular junction which has a muscle paralysis-like effect. Yes, you read that right: Botox in a bottle! These ingredients work by reducing muscle contractions, which in turn can reduce wrinkles.

The less your facial muscles move (especially around the eyes) the less wrinkles can be formed.

An example of a carrier peptide cosmetic is The Ordinary’s Agireline Solution 10%

Neurotransmitter-inhibiting peptides Examples

Acetyl hexapeptide-3 Common name: Argireline

Inhibits SNARE complex formation and catecholamine release.

Pentapeptide-18 Common name: Leuphasyl

Mimics the natural mechanism of enkephalins and inhibits neuronal activity and catecholamine release.

Pentapeptide-3 Common name: Vialox

Competitive antagonist at the acetylcholine receptors.

Tripeptide-3Common name: Syn®-Ak 

Mimics the effect of Waglerin 1, a peptide that is found in the venom of the Temple Viper.

Clinical Evidence

The efficacy of peptides in cosmetic applications is supported by a growing body of clinical research. Studies have demonstrated that formulations containing signal peptides can lead to significant improvements in skin elasticity, hydration, and wrinkle depth over periods ranging from several weeks to a few months.

Carrier peptides, particularly those delivering copper ions, have been associated with enhanced wound healing and overall skin appearance.

Neurotransmitter-inhibiting peptides have shown promise in reducing the appearance of expression lines, offering a non-invasive alternative to botulinum toxin (botox) injections.

However, it is important to note that the magnitude of these effects can vary based on peptide concentration, formulation stability, and individual skin characteristics.​

Regulatory Status

Peptides have a well-established history of safe use in cosmetic products. Regulatory agencies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), classify peptides used in cosmetics as generally recognized as safe (GRAS) when formulated appropriately.

Manufacturers/the responsible person (RP) are responsible for ensuring product safety through rigorous testing, including assessments for skin irritation, sensitization, and stability. While peptides themselves are considered safe, it is crucial to evaluate the overall formulation, as interactions with other ingredients can influence product safety and efficacy, cosmetic product safety reports (CPSRs) are a key document in fulfilling safety requirements for all cosmetic products.​

Formulation Considerations

Incorporating peptides into cosmetic formulations requires careful attention to factors such as peptide stability, bioavailability, and synergistic interactions with other ingredients. Peptides are susceptible to degradation by enzymes and may have limited penetration through the stratum corneum.

To address these challenges, formulators often employ encapsulation techniques, such as liposomes or nanoparticles, to protect peptides and enhance their delivery into the skin. Additionally, combining peptides with other active ingredients like antioxidants, hyaluronic acid, or retinoids can amplify their efficacy. Ensuring an appropriate pH and using stabilizing agents can further maintain peptide integrity throughout the product’s shelf life.​

Some peptides may be too large to deliver topically, therefore, studies on peptide permeability coefficients should be conducted.

Feedstock Considerations

Natural Sources

Peptides from natural sources are isolated from sources such as plants, milk, or muscle proteins (e.g., beef, chicken, pork, fish). Examples include soy oligopeptides (from soybean proteins), silk peptides (from silkworm silk glands), and rice peptides (from rice protein). Sourcing from natural sources can be more sustainable, but it’s important to ensure responsible farming and harvesting practices. Many cosmetic brands choose to be 100% vegan, therefore, animal derived proteins cannot be used.

Synthetic Peptides

These peptides are created in a laboratory using chemical reactions. Recombinant DNA Technology is a technique where peptides are produced by genetically modifying microorganisms or cells are used to produce specific peptides. Synthetic peptide production can rely on petroleum-based feedstocks and energy-intensive processes, which cantering with it environmental concerns.

Cultured Peprides

Cultured peptide production involves culturing cells to produce peptides, potentially offering a more sustainable and scalable approach. This method can be more sustainable than traditional chemical synthesis, but requires careful consideration of the materials used for cell culture and the energy required for the process. It’s typically less labour intensive than sourcing peptides from natural sources and does not require much land, unlike natural sources.