Peptides are getting very interesting.

As far as cosmetic chemists go, I’ve always been less interested in the headline actives and more focused on getting the base right.  I didn’t adopt that position strategically, it was just a natural fit given that, after careful analysis, I felt that most of the cosmetic actives people were getting excited about were typically 80% hype and only 20% scientifically valid.  However, it looks like that balance is finally shifting, at least in the peptide space and if the recent flood of R&D papers is anything to go by, peptides could soon be helping us to re-grow all sorts of damaged tissue.  The era of the bionic person is nigh.

Without going into a complex lesson in biochemistry (which I’m not qualified to do), peptides are signalling molecules, made of amino acids (the same stuff that makes up proteins, the stuff that makes up around 20% of your lean body mass, another 60% being water and the rest a mix of stuff including your bone minerals). Amino acids arranged in certain shapes and sizes can act like keys for a range of biological processes. In the cosmetic space some of these processes include the key to unlocking collagen synthesis, elastin arrangement, melanin production, inflammation and barrier protection.

In cosmetic science we use peptides that are synthetic or man-made, the exact shapes and sizes we use don’t exist naturally. Peptides are manufactured this way to give them a better chance of reaching the target tissue (don’t forget that in real life, peptides are produced close to the site of action whereas ours have to be able to penetrate the rather tricky epidermal barrier as a minimum), of being stable outside of the skin environment (to that they can be supplied), to better control delivery over a period of time and to reduce toxicity.  The down side about all of this work is that it is expensive. Peptide synthesis requires lots of high-tech science equipment and knowledge, refining the molecule shape and running testing is also time consuming and costly and coming up with novel anti-ageing technology is financially lucrative and is therefore always protected by patents and other instruments.  So all up you typically pay (todays prices) at least $1000 AUD per Kg for a cosmetic peptide, as supplied, and most manufacturers supply them in presentations that require a dose rate of between 0.5-3% in a formula, that means a per-formula cost of at least $5 per Kg from one ingredient but more typically $15-$30 per Kg on top of other costs.  To put this into perspective, a smallish to medium-sized brand with a cosmetic night cream that contains some natural ingredients typically comes in at around $40 per Kg for ingredients.  In that scenario it isn’t un-heard of for your peptide input to account for between 50-80% of your overall formula costs.

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If we focus back to the structure again we can think of the peptides we use in cosmetics as having two regions to do two different jobs. There is the functional ‘key’ part which is the bit that interacts with whatever biological process we wish to influence, then there is the tail part which is the man-made ‘motor’ part if you like, the bit that gets the peptide to where it has to go.  Typically this ‘motor’ part has been a fatty acid onto which the amino acids that form the peptide can be attached.  These fatty acid chains can be sourced from any feedstock, vegetable or mineral with saturated C16-C18 chains likely coming from palm (although not always).

Here is what Matrixyl 3000 look like. Chemically this is now known as Palmitoyl Pentapeptide-4.

Image by: Ed (Edgar181) – Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=37953266

Palmitoyl – palmitic acid tail, the ‘motor’. The name palmitoyl doesn’t mean it comes from palm, it means that it is a 16 carbon fatty acid.  Lots of vegetable and mineral origin materials have this configuration.

Penta – means 5. Because this is referring to the number of amino acids that make up the peptide chain, in this case, a lysine rich blend.

The number 4 at the end is an arbitrary number that is assigned by INCI regulators when the molecule is first listed so lower numbers were most likely registered earlier than larger numbers – this way of attributing numbers is not unusual, many (but not all) numbers you see in INCI names are about when the ingredient was registered. This is one reason why I find it amusing when people say they don’t want chemicals with numbers on them as that means something bad.

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Matrixyl 3000 came onto the market in 2000 and it has remained popular because it does work quite well as long as it reaches its target tissue – it stimulates collagen, fibronectin, elastin and Glycosaminoglycan production. It also has a high level of market acceptance and awareness and is relatively widely available.

So where does it need to get to?

Collagen and elastin synthesis happens in the dermis but can be triggered by signals from fibronectin. A dermatologist will give you a more thorough explanation of this.

Fibronectin is part of the extracellular matrix and is synthesised, in part by keratinocytes (whole story is here )

Glycosamionglycans include hyaluronic acid and this chemistry helps to support collagen and elastin health by, amongst other things, trapping moisture.

And does it work?

Having been in the industry for a while now I see what people buy and what they don’t and this is one ingredient that is still purchased with some enthusiasm.  If you were to ask a dermatologist if this works they would probably say ‘no’ or ‘maybe a bit’ because that’s quite a valid science-based response but from where I’m sitting, as a cosmetic chemist I do see people get results with this, maybe not measurable collagen boosting (I don’t know as I haven’t had anyone share those type of results with me) but it passes the visible-check test which means that a substantial amount of people feel it does something good.  The gap between dermatologist and cosmetic efficacy is the evidence gap.  While cosmetic peptides have to go through some testing, that testing is typically carried out in small trials (20 people or less most often), by the ingredient manufacturers in short term trials (up to 60 days).  Dermatologists have medical degrees and as scientists we are taught to look for more robust evidence than this, especially when it comes to mapping cause and effect.  What I think is happening with this peptide is that it is helping to really boost moisture levels and take some of the stress that dryness brings away.  At least here in Australia where there are a lot of crispy skinned white people, that’s quite welcome and does give visible improvements regardless to how well the molecule penetrates or not.

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But that’s old, what’s new?

If I put the rather clunky term ‘peptide skin’ into DEEPDYVE, an online  scientific paper resource, I get 322 papers pop up that were published in 2019 alone, many of which have some direct relevant to the cosmetic space.

Hot areas of research include the use of peptides to re-construct badly damaged skin such as full-thickness burns and other traumatic injury.  Some particularly interesting advances have been made in using self-assembling peptide nano fibre hydrogels to help stimulate the growth of bone and cartilage, heal complex wounds and better deliver drugs.  Some research is even looking at using peptides to help repair the type of nerve damage that results in hearing loss!  Now while not all of these applications relate to cosmetics, the technology is transferable.  The use of peptide infused hydrogels is particularly interesting to me as that’s essentially a super-powerful serum, the type that we commonly use in cosmetic science. It is likely that the learning from this type of research into partial thickness burns, ulcers and surgery wounds will filter up into cosmetic science and inform peptide manufacturers of the technology needed to get results at a ‘maintenance’ level in the cosmetic space.

In terms of the peptides that are currently available to the cosmetic chemist, there’s lots on offer with 344 results generated from a ‘peptides’ in ‘cosmetic ingredient’ search on the 2019 ‘In Cosmetic’ site alone.  Now I haven’t looked in detail at all of these but I know, from what I have seen, that some of these options have evidence that is a little light on scientific rigidity while others are a bit more robust.

How can you tell if the evidence behind a peptide is good?

Ok so I don’t want to give you an analytically perfect way to do this as for most of you, that won’t be practical. Instead, what I want to do is just show you what you can do to discern information about peptides a little better. Here is my list of what I do when I’m checking.

First I have to assume that the chemistry is relatively stable and able to release the peptide into the ‘skin’. I say the word ‘skin’ very deliberately as I don’t think we can assume that the peptide will get anywhere very deep unless we formulate very specifically for trans-epidermal delivery, something that we can only really know we’ve done if we measure it (and that gets expensive).

Once that’s acknowledged I do this. 

1. In vivo is better than in vitro.

In vitro is the test tube testing.  Skin cells in a petri-dish or equivalent are a useful medium to test if a peptide can do something on the cells it is targeting.  However, just because it can do something in a test tube or Petri dish doesn’t mean it will do it in a biological system. Further, the ingredient MAY be able to do something to these target cells in real-life but if you can’t see any benefits from that action it is not very useful cosmetically, at least not in the short to medium term.   What I do is look to see how many of the ingredients claims have been seen on real people during normal or typical use.

2.      Sample size, duration and type.

How many people were tested on, for how long and using what type of product?  I mentioned in an article I wrote the other day that the EU is now tightening up on product claims and then I focused on ‘free from’. They are also tightening up on claims made by brands  based on the ingredients they are in the formula, the actives.  If you are looking to use a peptide in your product so that you can piggy back on the data the manufacturer has put together for your claims, you must make sure that your product is equivalent. That means a very similar base formula, active at the same level and same in-use protocol.  If I’ve got a customer who wants a peptide spritzer I can’t use the data generated by the supplier using a cream and claim equivalence.  Also if I only have the budget to add 0.5% of peptide but the manufacturer formulated with 2% I can’t expect the same results.  It’s not rocket science but in the thrill of it all, this type of thing can get lost.

3.    How the peptide claims to work.

Peptides can claim all sorts of exciting things but what I do is have a pragmatic look at what they are saying, focusing on where the active has to get to do what they claim.  Topical botox type claims are very, very tricky to achieve via a cosmetic due to the action of the peptide needing to affect muscle contractions.  Hydration claims only have to get as far as the epidermis,  pigmentation claims only have to get to the keratinocytes in the epidermis.  The site of action gives me some idea of how critical my base formula design is in achieving the promised action.  If the action is expected on the surface, I only have to get my product to sit their, if it is at the muscle layer, I need some heavy duty skin penetrating boosters to even have half a chance. Some ingredient philosophies identified by the brand owner may make it very difficult for me to achieve a base product that can even attempt to deliver this active correctly.

4. Price per dose.

Yes, it’s exciting to come across a new ingredient with the promise of a peptide but does it stack up financially?

5. Time to act.

This is another thing I carefully look at.  If the brand I’m working on is the type of product range you take home and love forever then a longer action time may be OK, especially if the claims are not over-sold.  However, if I’m working with an attention-deficit brand that you stack high, sell bucket loads of then move on, the action has to be faster.

6. Availability legally and practically.

There is no point in getting excited about a chemical that you can neither purchase in pack sizes that you can afford or it is not approved for use in your country.  I have to check both and as these things can both be show-stoppers its good for you to check this also.

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Peptides – wrapping it up.

As a scientist I used to be very skeptical about cosmetic peptides as I saw a lot of companies launching a lot of products that had not a lot of transferable data behind them.  In addition, many were going for that ‘topical botox’ type angle and failing to live up to it in real life.  However, nineteen years have passed since Matrixyl, a peptide that is still going strong, and in that time, our scientific understanding of the value and application of peptide technology has grown, our ability to synthesis functional peptides has improved as too has our ability to formulate for better results.  So while it may not always work out that the peptide you purchase for your skin care brand works in the optimal way as highlighted in the glossy brochure, there is every chance that it will do something good and that you will see some level of results if the ingredient is used properly.  Now whether it is worth it depends on many factors but I am now of the opinion that at least it is now worth a try.  As for the non-cosmetic use of peptides, that’s got me really excited.  How cool would it be if we could re-grow our own tissues after sports or age related injury or stress?  I think that would be wonderful and if cosmetics can piggy back on some of that, why not!