Peptides in cosmetics
Peptides, the skin’s natural messengers
Peptides are used everywhere in cosmetics. From skin care and hair care to body care and sun care.
Around 7 600 new products, dedicated to cosmetics containing peptides, are launched every year around the world*. One of the main reasons for this is that peptides work.
But not all peptides have the same function. It is important to understand that only very specific endogenous peptides are involved in cell metabolism as upstream regulating messengers.
It works like a key and a keyhole. Specific peptide sequences trigger specific protein production, and when it comes to skin proteins like collagen or elastin, the beauty possibilities are clear.
As the forerunner in peptide development for cosmetic applications, Croda Beauty Actives has developed a full range of peptides to answer various beauty concerns.
The guaranteed efficacy of our peptides is proven through rigorous scientific testing.
*Source Mintel GNPD
Group Assisted Purification Peptide Synthesis (GAP-PS), a better way to manufacture peptides:
This hybrid system takes the best of well-known liquid and solid processing technologies and allows to chemically produce peptides more rapidly, with fewer solvents (including water), with higher yields (100% purity) and hazardous waste reduction. This technology tackles the traditional challenges of peptide manufacturing to make complex synthetic peptide manufacturing more easily scalable, economical, and sustainable for large-scale production.
Using published data from a prominent peptide CMO, we completed a detailed, comparative assessment between GAP-PS and SPPS. Choosing an example 5-mer peptide as the basis for comparison, we analyzed costs per coupling step across methods. Key savings estimates identified in that 2019 comparison included >80% reduction in anchor cost achieved by replacing the SPPS resin with the GAP protecting group. Currently, compared to SPPS, estimates show GAP-PS reduces solvent costs by >60%. In total, it is estimated today that GAP-PS can reduce raw material costs by more than 50% and is estimated to reduce labor cost by 30-45%. These estimates are, of course, intended to provide a benchmark and can vary depending on the specific target.
Because GAP-PS coupling reactions are highly efficient, deletion / insertion impurities are rare. This translates to higher crude peptide purity, which can further reduce production costs during chromatographic purification. In some cases, such as for cosmetic products, the crude purity is sufficient, and chromatography is not needed.
Assessing solvent efficiency, GAP-PS runs near the saturation point of the chosen solvent compared to SPPS – which can require large amounts of solvent not only for resin suspension and swelling, but also for resin washing. GAP-PS effectively utilizes green solvents such as ethyl acetate and 2-MeTHF for synthesis because GAP-PS is not restricted by the need to adequately swell a resin support.
Compared to SPPS, GAP-PS also improves on throughput: the GAP anchor has a peptide loading of > 3 mmol / g, which is 2 – 3 times the value for the best SPPS resins. GAP-PS loading, along with the solvent benefits, means reactor and facility utilization is increased. GAP-PS also compares favorably with other solution phase methods in terms of process time; aqueous extraction steps are minimized, with phase separations taking < 2 min on average for a 4 L scale.
Operationally, reactions on a large scale generally take longer than when on bench scale. Also, the peptide product must be stable under reaction conditions for prolonged periods to allow for in-process controls. To address this, GAP-PS facilitates flexible coupling and deprotection reactions. For example, Fmoc deprotections can be finished in as little as 10 minutes, but can also be stable for longer than 3 hours if needed. There is also flexibility with temperature control for coupling reactions, to balance throughput vs. energy costs according to customer requirements.
To enable in-process analysis, GAP-PS reactions can be quickly and easily monitored using standard HPLC and LC-MS techniques at any point. SPPS often must rely on qualitative measures which can take hours before results are generated.
These are just some of the aspects GAP-PS addresses for large scale production. Please contact us to discuss your specific target if you are interested in scaling up. GAP-PS has relationships with a variety of reputable CMO’s for large scale synthesis, where GAP-PS can be licensed during tech transfer.
Due to reaction efficiency, impurities are minimal and crude purity of the desired peptide is high. This reaction efficiency yields more product per reaction volume and reduces purification processing and waste materials – resulting in lower processing costs.
The GAP-PS approach creates significant economic advantages due to reduced consumption of raw material and reduced purification costs. The process avoids CMR substances and supports sustainability by reducing the usage and waste of hazardous chemicals, even enabling recycling of reaction solvent in some cases.
Synthetic biology to produce cosmetic peptides:
Advanced development programs allow the manufacture of peptides without the use of solvents (except water) through new routes, via synthetic biotechnology, in particular from algae. Synthetic biology is a multi-disciplinary field of biotechnology that combines biology, bioinformatics and engineering to build and develop biological systems that do not exist in nature, or to reconstruct existing systems by modifying them. This novel approach allows the development of production alternatives for molecules, like peptides, that have traditionally been manufactured using particular chemistries that may have relied on solvents, catalysts or environmentally unfriendly materials. Synthetic biology also makes it possible to improve some manufacturing processes in terms of time savings or yields, reducing consumption and costs. At Croda Beauty, we are pleased to offer the first peptide obtained thanks to synthetic biology: Kerabio™ K31 the first-ever recombinant hair repair protein from an ingredient supplier.
Peptide encapsulation for targeted delivery
Unlike other hero cosmetic ingredients, like retinol or vitamins, peptides are not prone to degradation and toxicity. The benefits of encapsulation are known for retinol and vitamin C, reducing their degradation and sensitisation. Peptides do not present similar issues and are more tolerable by different skin types, however, these molecules can also benefit from controlled release and targeted delivery.
Peptides can promote different benefits to different layers of the skin but delivering them to the correct target can be a challenge. This challenge can be met with innovative delivery systems that allow peptides to increase stability and effectiveness, and target specific skin layers. For example, peptides that have the epidermis as the site of action can be delivered using novel lipid capsules. Innovative approaches vary in terms of benefit given by the delivery systems. Today, we have lipid delivery systems available that are naturally derived, biodegradable and highly stable.
Example of peptide encapsulation for optimal delivery to the epidermis. Case of Crystalide™
Older delivery systems like liposomes are sensitive to surfactants and are usually unstable in emulsions. The latest generation of lipid systems, consisting of a central oil core surrounded by a mixture of lipids and waxes, circumvents this issue and facilitates the incorporation of peptides in final formulations.
Delivering peptides to the skin’s specific targets can be achieved with deep understanding of the biological effects of the molecule, as well as its physico-chemical characteristics. Unique and specific design of delivery systems, like submicron particles, can allow protection and stabilisation and at the same time control the release, increase the activity, and reduce issues.
*Number of owned publication in third party media
*Number of peptide-based products manufactured Croda Beauty Actives