Peptides in Cosmetics – The evolution of Natural compared to Synthetic

Introduction

Peptides composed of amino acids and of different lengths, are most often designed and chemically synthetized by reproducing the amino acids sequence of the binding site/domain/s of specific proteins targeting biological mechanisms through or not receptor interaction involved in skin/hair biology.

Specific expertise is needed in design:

1. Short sequence peptides, mostly in linear form, to reduce cost. This sequence is designed reproducing existing eukaryotic peptides and/or proteins domains. Artificial Intelligence is nowadays helping with design.
2. Fatty acids chain tails to be attached to the carboxyl end, due to instability and poor skin barrier penetration, therefore the idea of a) the fatty acid chain to help penetrate the lipidic bilayer and b) reduce the access of proteases that would eventually degrade the peptide.
3. In vitro testing to prove the specificity and the activity of the peptide for the mechanism of action that is targeted (cellular models are often used).
4. Safety Clinical testing to demonstrate the lack of irritation and immunogenicity of the peptide on skin (therefore repeated patch test is often needed).
5. Clinical testing in humans (due to the ban on animal testing), requires expertise in selecting the right population as well as proven capacity to measure the outcome instrumentally.

More recently, due to a push on naturality, the look for natural occurring peptides has been a priority for the cosmetic industry.

Natural Peptides

Natural peptides extracted from plants have been identified a long time ago (1). Their role is often associated with protection against pathogens, or they are used by the plant as signaling molecules for the regulation of growth and development. They can be of linear or circular form. They can be of different amino acids lengths. Antimicrobial peptides containing cysteine knots, both in the linear and circular conformation, are resistant to the attack of proteases and therefore would have a longer half-life in biological systems. These peptides are of particular interest for pharmacological and cosmetic applications (2).

Different than peptides derived by protein hydrolysis targeting nonspecific biological mechanisms, plant peptides are not derivatives but synthetized by the plant for specific needs.

Extract-rich or purified plant peptides can be commercialized for different benefits, from anti-aging to skin tone regulation, antioxidant, anti-inflammatory, etc. (3, 4).

The efficacy of these extracts would depend on the specific concentration of the peptides fraction in the final extract.

Purification from the plant could be an alternative, but the relatively low concentration of these peptides in plants would require a huge amount of raw extract to start with.

Synthetic peptides have often been designed to reproduce specific sequences/domain allowing a relatively short peptide length (typically 2-6 amino acids) and therefore can be produced cost effectively. With the exceptions of some signaling and antioxidant peptides (4), natural peptides are often composed by a longer sequence of amino acids (24+) and therefore are not cost effective to produce by synthesis.

Some plants with relatively high concentrations of these longer peptides have been identified (2). It would be possible to use extracts from these plants or alternatively to purify out their peptide fraction. Initial testing of these extracts has shown a high level of toxicity in vitro (Dell’Acqua G, unpublished), probably associated with the presence of alkaloids in the extracts, therefore reducing the relative concentration useful for testing (including the peptide fraction) and the overall probability of having a viable safe and effective extract for cosmetic applications. On the other end, it would be possible to purify the peptide fraction if this effort would deliver a cost-effective peptide with a reasonable yield. This hypothesis needs to be verified.

Finally, synthesis of plant peptides (bio-mimetics) would need to be optimized for cost and scaled up for production. If synthesis of circular peptides is needed, specific cyclization steps could be tricky, costly and non-specific. A final single isoform would need to be optimized as the final product, and additional purification would be needed.

Once plant peptides are obtained, testing for safety and efficacy would need to be run to ensure a similar performance than the synthetic counterpart. Skin penetration would also need to be assessed. On a positive note, stability could be an advantage compared to synthetic peptides, when considering cysteine knots peptides.

Conclusion

Although a push for naturality would support the introduction in the cosmetic market of plant derived peptides, technology around their production is still in its infancy. The potential of these peptides could be relevant once human targets are identified and possible novel mechanisms of action revealed. The substantial annual growth of clean beauty products in the market, allowing safe chemicals and naturals to co-exist in the same formulas, would be the best playground to test plant peptides and synthetic ones together to understand possible benefits in synergetic complexes.