What are peptides?

Peptides are short-chain amino acids, the building blocks of proteins and enzymes. For example, collagen peptides are obtained by hydrolysing collagen, and they contain the repeated sequence of three amino acids: proline, glycine, and hydroxyproline. Collagen, as the main constituent of skin, comprises nearly 70%-80% of the weight of the dermis and the matrix of collagen and extracellular protein could allow for both structural support and elasticity of the skin.  Researchers using computational 3D modelling of proteins having important functions like enzymes, such as superoxide dismutase, help find the short sequence in the protein responsible for the function. Thus, peptides can be easily synthesised and function similarly in the cells as the whole enzyme and proteins. Therefore, there is a growing interest in using peptides as nature-derived active ingredients in various cosmetic formulations.

Due to the high water solubility, sensitivity, and cost, using peptides in skincare is not straightforward. The primary challenge with dermatologically active peptides lies in delivering them to the site of action. Unlike other drugs, peptides cannot be administered orally as they are digested for absorption and are not stable in aqueous solutions for long. Most peptide drugs are, therefore, administered intravenously. Moreover, peptides, with molecular weights typically exceeding 500 and being water-soluble compounds, cannot penetrate the lipophilic cell membrane or the waterproof upper layer of the skin, the epidermis.

How can we deliver peptides to the skin?

Despite the challenges, there are promising methods for delivering peptides to the skin cells. One such method is chemical derivatisation, which involves forming an amide bond with lipid-soluble long hydrocarbon chain fatty acids, like palmitic acid. Although this process increases the size of the molecule, it also makes it lipid soluble, enabling it to penetrate the waterproof layer of the epidermis. Studies on the palmitoyl dipeptide and palmitoyl carnosin (palmitoyl-β-Ala-His) have shown that less than 10 to 4% of the initial radioactivity accumulated below the dermis within 6 hours, indicating no significant transcutaneous penetration and therefore, no uptake into the blood or lymphatic fluids. [1]  . In cosmetics, systemic activity is not desired, but we want to get the peptides to the skin cells in the epidermis or dermis. The potency of other palmitoyl peptides, such as in the Matrixyl 3000 patented and used in No 7, has also been clinically proven [2].

The other approach is to use the peptide without derivatisation but develop special formulation methods and deliver them deeper to the epidermis. Several methods have been described using lipid nanoparticles, polymeric nanoparticles, hydrogels, functionalised surfaces, and DNA- and RNA-based delivery systems[3].

 Liposomes are small spherical vesicles composed of cholesterol, which modulates membrane rigidity, and non-toxic amphiphilic phospholipids that assemble in bilayers and whose composition tunes their physicochemical and biophysical properties. The liposome's aqueous core and lipid bilayer allow the loading of hydrophobic and hydrophilic drugs. Liposomes are biocompatible and biodegradable nanocarriers.

Micelles are spherical nanocarriers composed of surfactants that self-assemble in single-layer lipid vesicles. The hydrophilic peptides are attached outside the micelles.  

We can also use hydrogels to deliver water-soluble active molecules. Hydrogels are networks of natural (for example, hyaluronic acid or alginate) or synthetic polymers (for example, poly (ethyl acrylate-co-methacrylic acid) or  poly(N-isopropyl acrylamide crosslinked polymers that can retain a high water content (typically 70-99%) and maintain a three-dimensional configuration.

The most modern technology is mRNA technology, which delivers higher molecular-weight peptides and proteins into the cells. The Nobel Prize for Katalin Kariko recognised this technology for developing vaccines for Covid-19.

 How do peptides work on a cellular level?

Currently, there are a wide variety of peptides available as cosmetic ingredients, which can be categorised according to their mechanism of action [4] [2]:

These are signal peptides, which stimulate matrix protein production (such as collagen and elastin) and cell growth, amongst other cell metabolic functions (for example,  Palmitoyl Tetrapeptide-7, Palmitoyl, Pentapeptide-4);

The carrier peptides may act as transportation facilitators for important substances or trace elements inside the cell, such as copper and magnesium (for example, Tripeptide-1, GHK-Cu);

Neurotransmitter-inhibiting peptides may target expression wrinkles by inhibiting acetylcholine release at the neuromuscular junction by acting on distinct molecular targets (for example, Acetyl Hexapeptide-8, Acetyl Octapeptide-3).

There are enzyme-inhibiting peptides, which may reduce the activity of enzymes that participate in skin ageing (for example, soybean peptides which inhibit serine proteases and silk peptides, which inhibit tyrosinase).

 What are the anti-ageing skin benefits of peptides?

Peptides promote hydration and collagen production, which are responsible for the skin's firmness and elasticity. Peptides may affect the skin barrier function. They may stimulate cell turnover, leading to smoother and more radiant skin. There are also anti-inflammatory peptides that help reduce redness and skin sensitivity.

How do we use peptides in KlaraSkincare products?

The above-mentioned synthetic peptides are usually applied in very low concentrations (less than 0.005%). As our products were designed for mature skin, when collagen production is significantly reduced, the aim was to replenish the collagen by applying 3% collagen peptides in our day cream, night cream, and award-winning light day cream. As far as we know, no other product on the market contains this high peptide concentration. Without our trademarked bio-mimetic micelle technology would not reach the skin cells. To deliver such a high concentration, we use plant-derived phosphatidylcholine (Soya lecithin) and prepare micelles using low molecular weight hyaluronic acid to attach hydrolysed marine collagen peptides.

How do we know we created the micelles?

While liposomes are 20nm to 100 nm in size and appear as milky solutions, not transparent, micelles are much smaller and form transparent solutions. We must turn our milky solutions into semi-transparent micelles with high marine collagen concentrations.

At KlaraSkincare, we use palmitoyl derivatives for active peptides, such as Matrixyl 3000, in our powerful serum, which is combined with Swiss apple stem cells and Eye contour cream. We also use high concentrations of collagen peptides attached to micelles. 

We ensure that the micelles are locked into a double emulsion of water dispersed in oil in water-washable face creams. We also attach botanical active extracts containing antioxidants and cold-pressed plant oils. Many have weak natural sun protection properties, such as Raspberry Seed oil. We work hard to avoid synthetic ingredients and never use them above 1%. Our creams contain very high concentrations of natural peptides that must be preserved using potent preservatives to achieve a 12-month shelf-life.

How to use our anti-ageing high peptide content products?

To achieve the best results, always apply the creams after thorough cleansing. The bio-mimetic micelle technology may help penetrate the dirt deeper, causing breakouts if we ignore this important step. Use our micellar water or the special Sea Buckthorn Face polish, prepared using only raw ingredients, cold-pressed plant oil, bamboo and jojoba grains and CO2 extract of Sea Buckthorn, Vanilla and orange peel.

For best results, you must repeat the skincare routine twice daily to plump the fine lines and wrinkles and slow down the skin ageing. Healthy and radiant skin looks younger!

References

[1]        K. Lintner and O. Peschard, “Biologically active peptides: From a laboratory bench curiosity to a functional skin care product,” Int. J. Cosmet. Sci., vol. 22, no. 3, pp. 207–218, 2000, doi: 10.1046/j.1467-2494.2000.00010.x.

[2]        M. S. Ferreira, M. Catarina, J. M. Sousa-lobo, and I. F. Almeida, “Trending Anti-Aging Peptides,” pp. 1–15, 2020.

[3]        A. Cesaro, S. Lin, N. Pardi, and C. de la Fuente-Nunez, “Advanced delivery systems for peptide antibiotics,” Adv. Drug Deliv. Rev., vol. 196, pp. 1–58, 2023, doi: 10.1016/j.addr.2023.114733.

[4]        F. Gorouhi and H. I. Maibach, “Role of topical peptides in preventing or treating aged skin,” Int. J. Cosmet. Sci., vol. 31, no. 5, pp. 327–345, 2009, doi: 10.1111/j.1468-2494.2009.00490.x.