Penetration enhancer for actives in a mist

Hi everyone, 

I am trying to formulate a mist with actives. I know this is not the most effective way to include actives in skincare, but I just want to try for experience. 

What penetration/delivery systems do you recommend? An example would be oligopeptide-1 in a mist. I am fully aware that not enough research is behind most peptides, but again — just for experience. 

If I included water, glycerin, malachite, and oligopeptide-1 in this mist, how could I improve effectiveness on the skin? I am really talking about penetration — is dimethyl isosorbide a good option? What other info do I need to know in order to proceed with this type of formulating?

Thank you as always!

Comments

  • Personally i feel that if you choose to use peptides, perhaps it would be good to have it suspending in a serum thickened with a water based gelling agent. 

    If you choose to use it in a mist, perhaps normal Glycols or Diols would be fine?
  • PharmaPharma Member, Pharmacist
    So, oligopeptide-1 is, allegedly, EGF... just 10 times shorter... in other words, it's inactive. Assuming magic still existed and that thing really had some biological activity, what you'd need for penetration/delivery system is not using a mist but a syringe or, which would come very close to a mist, a 'mesotherapy gun'.
    What might work as well are solid nanoparticles, liposomes, and the like though good luck loading them with enough oligopeptide and determining whether or not they get out of there at the right place in the right quantity.
    My advice: Oligopeptides on skin are usually pixie dust and only good for marketing, nothing more. You certainly agree, marketing does not need a penetration enhancer but using one would likely boost marketing. Go with something which has a nicer smell than dimethyl isosorbide (which is not helping with most oligopeptides, anyway). Are you going to sell that mist or do you make it for yourself?
  • I read that DMI works for oil rather than water soluble actives. I am sure someone  mentioned it on chemistcorner too (run search function). On this other hand the Ordinary sticks it in every second formula most of which are aqueous serums. I don’t know if what they do can be considered best practice though. I think for a spray your best bet is propylene glycol. Keep in mind that you should be careful with penetration enhancers because our skin has a barrier function for a reason and by delivering active ingredient deeper to skin you step into drug  territory. Only do it if you know exactly why you are doing it. Some actives must stay on the surface too.
  • Dimethyl Isosorbide is my ABSOLUTE favorite penetration enhancer. In my experience it works an absolute charm with water soluble ingredients (I use it with Niacinamide, Arbutin, NAG, Licorice.)
  • Unfortunately it's expensive.
  • Thank you all for your answers!

    I know that oligopeptide-1 isn't well-researched at all — I just want to try formulating with peptides fro experience. 

    I think I'll keep dimethyl isosorbide, but what other penetration enhancers will help molecularly small enough actives reach the dermis? Since I'm not selling I'm not worried about marketing rules/drug claims. 
  • Squalane and Propanediol are said to be penetration enhancers. And Glycols. Maybe Propanediol can play both a humectant and penetration enhancer role in your formulation. I absolutely love it because I find it to be an extremely effective (and simultaneously non sticky!!) humectant. It's also seemingly more "conditioning" than other humectants in my experience.

    Where are you getting Malachite from?

    And is this mist inspired by NIOD Superoxide Dismutase Saccharide Mist?
    I love that product and use it daily.
  • Personally, I would not use a penetration enhancer at all. In theory, if you have an active peptide there that will bind with the EGF receptor you can totally just have a topically applied product with no enhancer. On your side is the size of the peptide and the fact that the receptor it would bind to is trans-membrane. This means you will just need a formula which is very compatible to your peptide and keeping it active. 

    Adding a penetration enhancer could possibly reduce your activity if you're not using something compatible.


  • PharmaPharma Member, Pharmacist
    1: That receptor, should your polypeptide bind to and activate it, is beneath the uppermost dead skin layer. A penetration enhancer seems reasonable.
    2: Your polypeptide is likely (Do you have the amino acid sequence? I couldn't find it) water soluble and hence, a penetration enhancer for lipophilic molecules won't do any good. Maybe one which disturbs lipid layers, think oleic acid or glyceryl oleate, might work. Urea looks good at first glance but it's bad for the polypeptide. DMSO would be my pick (I'm a pharmacist, so no restrictions for me LoL).
  • Thanks everyone!

    Yes, Emma, it was inspired by NIOD's SDSM. I love it too :)

    Pharma — thank you for your answer. I don't know the amino acid sequence, but it is polar, so water-soluble. I want to try glyceryl oleate, but can you think of any other substances that disturbs the lipid layers of the skin?

    I though dimethyl isosorbide did just that — disrupts lipid organization, so that active ingredients can travel past the stratum corneum. 

    In other words, what are some penetration enhancers that are water soluble and compatible with medium/large peptides?
  • I got Malachite from Gattefossé. 
  • PharmaPharma Member, Pharmacist
    Found what I was looking for (assuming we are talking about the same ingredient sh-oligopeptide-1): CLICK
    So, it's a GMO full length EGF which has a his-tag. The peptide lacks any activity if applied dermally, I cite: Danger of toxicity minimised by lack of transdermal absorption. Topical product only with no potential for abuse.
    The oligopeptide-1 and EGF are fairly long and will really not penetrate skin with common penetration enhancers (as mentioned before, you'd need the super fancy stuff, glyceryl oleate and co won't do the magic). However, because it's a full length human EGF (the his-tag is likely not going to disturb activity, it's just there for simpler purification over a zinc-dotted column), it will be active once through stratum corneum. EGF can be applied to ulcers where that protective layer is lacking and it looks as if it would speed up healing = it works. Now, there is one major drawback with uncontrolled use of EGF: Skin cancer! If the producing company weren't a 100% sure to sell a completely inactive product, you could sue said company for a large amount of money should you get, one day in the future, skin cancer on a skin area where you, in the past, had applied their product even if just once. That's not a joke! Hyperactivity (uncontrolled, permanent activation) of EGF signalling is one of the mechanisms leading to cancer, activation can speed up transition from pre-cancerous stage to full blown cancer, and hence, inhibiting EGF receptors or EGF signalling is one of many new anti-cancer treatments (one of several example HERE).
    I'm not scaremongering and you may decide for yourself whether or not to believe me. For your information, I'm a pharmacist, did my PhD on inflammation (which has many things in common with cancer and cancer development, I used to work a lot with cancer cells, and employed different drugs for and against cancerous cells) in a group focussing on development and synthesis of new anti-cancer molecules (such as epothilones) and did my post doc on cancer prevention.
    If you really want to play games with your skin and your health, get a transdermal delivery device (CLICK) or search for 'hyaluronic pen injector' on Amazon (all you need is a sterile refilling technique for your peptide solution). It is a very stupid idea to do so but it's your best bet that it'll work (whether for or against you remains to be seen in about a decade). If you decide against such a strategy (which is the only reasonable decision), use whichever traditional penetration enhancer you like most because it will (likely/hopefully) not work.
  • Thank you, Pharma!

    Ah yes, I know about the skin cancer growth side of EGFs. I just bat it aside, but the lack of activity of EGFs otherwise is kind of disheartening — so . . . no EGFs for me (at least until I know of any benefit). 

    I find your past work really interesting. Thank you for answering my questions so far — I really admire your knowledge!

    Would you find any reason to add small peptides in cosmetics? Copper peptides? Other tripeptides/tetrapeptides?

    There is this one: G-NH2 (a monopeptide haha), supposedly a whitening cosmetic peptide. It has a molecular weight of 74 Da and inhibits multiple pathways in melanin synthesis. If I were to acquire this, and dissolve it in water (or whatever solvent), WOULD IT PENETRATE PAST THE S.C?

    There is the initial issue of getting past the lipid layers, but I read something that said that excess water on the skin enhances penetration. 

    I really am intrigued. Thank you for taking the time to help me!
  • I think what you may be referring to is that the more hydrated the skin is, the more permeable it is. That's what I've read.
  • Yeah. 
  • PharmaPharma Member, Pharmacist
    Wickers said:
    ...
    Would you find any reason to add small peptides in cosmetics? Copper peptides? Other tripeptides/tetrapeptides?

    There is this one: G-NH2 (a monopeptide haha), supposedly a whitening cosmetic peptide. It has a molecular weight of 74 Da and inhibits multiple pathways in melanin synthesis. If I were to acquire this, and dissolve it in water (or whatever solvent), WOULD IT PENETRATE PAST THE S.C?

    There is the initial issue of getting past the lipid layers, but I read something that said that excess water on the skin enhances penetration...
    Sure, hydration ;) . Amino acids and short peptides are moisturisers which I like to blend with other stuff. I can't comment on their effectiveness because I use blends (for several reasons) rather than just tacky cheap glycerol.
    Some amino acids and short peptides have other benefits such as buffering, antioxidant activity, or chelating metal ions such as iron or copper and thereby protect your product and maybe also your skin. However, this is rather pointless if you were to add it already with a metal on it LoL. But the deep blue colour of copper peptide is simply stunning :D .
    If you are about active amino acids, eat them! I can recommend beta-alanine especially for elderly people. If you feel fancy (and got the cash), use carnosine instead and get some extra benefits or go with cosmetic hypes and use carcinine (Alistin™) with a higher stability and increased skin penetration.
    There's a bunch of amino acid derivatives which I like too (again, more benefits from these if served in a shake).
    I still have my doubts that anything labelled 'cosmetic' does more than water, glycerol, and petroleum. Sure, there are exceptions like urea. Urea is nice and at higher levels has been shown to increase cell regeneration too. But the fancy part, it's either marketing or pharmaceutical (and pharma does not use short 'natural' peptides for a reason). Gamma-polyglutamic acid would be an atypical peptide-like polymer which works but it's not working in but on skin and not meant to interfere with receptors or enzymes. Some lipopeptides are fairly efficient... when it comes to surfactancy ;) .

    G-NH2 is indeed a monopeptide (it honestly never occurred to me that this is even possible since a 'normal' monomer would be called amino acid) or rather the amid of the most simple and cheapest amino acid glycine and correct, it has a 74 Da MW. Does it do anything? Dunno... probably not, it's too small. Penetration-wise, I'd guess judging from its structure that its about as good as lactic acid. Given that glycinamide is sold as HCl salt, we might compare it with sodium lactate instead. How to increase penetration: If you use the hydrochloride form, try a mix with an equal amount of urea (don't forget to adjust pH to ~6.2 and maybe add some triacetin or similar). Good occlusion will help too -> use for example a petrolatum based emulsion or a cling wrap after application. Goes for all water and alcohol/polyol solubles: it helps getting them deeper and faster into skin. This brings me smoothly to the third point...

    What @emma1985 said. The mentioned occlusion (reduced TEWL) does exactly that and, if you use a carrier rather than a plastic wrap, it does even a bit more. Petroleum works well for petroleum insolubles like glycinamide HCl but not for petroleum soluble ingredients.
  • Thanks, Pharma! A lot of interesting stuff said, and I agree with your points about amino acids. It's fairly annoying trying to work around penetration issues when, yes, glycerol is the golden standard for humectancy and petroleum for occlusion (only for existing, non-penetrating cosmetic formulations?). 
    Imagine if most cosmetic ingredients were 500 Da or less. 

    And I know — I make up excuses to use copper peptides simply because of the colour . . . not that I have any idea how to formulate with it.

    Can you explain about gamma-polyglutamic acid and how it "works" if it's not meant to penetrate to influence receptors/enzymes? 

    And a final question if you have time: does adding an emulsifier to water-based products increase its affinity to skin and to a small degree, help actives to penetrate past the lipid layers (given that they are small enough)? I don't think this is accurate . . .
    An example would be glycolipids as an emulsifier/stabilizer. Would including glycolipids in a formula help water-soluble actives to penetrate (because some actives are binded to the carbohydrate side of the glycolipid)? Would the lipid part allow the whole compound to penetrate the lipid layers? 

    Thank you as always for your help!
  • PharmaPharma Member, Pharmacist
    Poly-gamma-glutamine sold as Gamma-MAX by Bioleaders Corp. is a humectant allegedly better than hyaluronic acid, stimulates NMF production, has a unique skin feel, and has chelation properties. It's based on the slime molecule from natto and a bit like natural and biodegradable carbomer.

    An emulsifier reduces surface tension and thereby increases 'wetness' of water. Potassium linseed soap is traditionally used to soften calluses on feet. I suppose it's rather the unsaturated fatty acids which do the trick, less the fact that they are surfactants.
    If you want to use emulsifiers for your proposed mechanism, go with liposomes and the like ;) . Certain molecules profit from each other but there is no rule of thumbs. Such interactions can be calculated using COSMO-RS (annual fees for such programs are about 20 k)... Hence, you likely have to do trial and error formulations (and somehow measure your mixtures).
  • Thank you!


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