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Getting Under Your Skin

I develop cosmetics for a living specialising on topical skin care as opposed to injectables and other invasive solutions. In my professional life I am quite often asked,

How does a cream even penetrate into the skin? Doesn’t it just stay on the surface (being therefore useless)?

Most popular opinions on the subject are:

  • Nothing gets inside the skin, because it is our impenetrable protective barrier (and therefore you need to stick needles in your face and inject things or use laser, dermabrasion and radio waves to achieve any kind of effect), or;
  • Only very expensive cosmetics would be able to penetrate into the skin.

Here’s how it all really works.

One of the skin’s primary functions is indeed protection, and not every substance would be able to get through this barrier. But it’s not impenetrable either.

Your skin is not a space suit that can only be pierced with a needle or a laser beam.


There are substances, dermatological medicinal creams among them, that are able to get so deep through the skin that they reach the deep tissue layer! If you have a desk job or are into sports, you may have used at one time or another some non-steroid anti-inflammatory cream (Voltaren Gel, for example) to relieve joint and muscle pain. Had our skin been indeed an impenetrable shield, it wouldn’t have worked at all. Some topical creams (oestrogen or corticosteroid containing solutions, for example) can even have a systemic effect on your body, and the skin’s barrier is quite unable to prevent that.

So how is the penetration possible? Because of The 500 Dalton Rule. Here it is:

Any substance with molecular weight less than 500 Dalton can penetrate the keratinous layer and reach the deeper skin layer, dermis, without the aid of any enhancing methods.

If you apply any of such substances on your skin, you do not need to burn it with lasers or acids, stab it with needles, polish it with abrasive devices or do anything else that would break its barrier.

Cosmetology uses these substances a lot without any trouble or complications. And you know them, too — vitamin A (retinoic acid and other forms of retinol), vitamin E (tocopherol acetate), certain forms of vitamin C, caffeine, niacinamide, resveratrol, sodium hyaluronate, glycolic acid and most other AHA-acids, salicyl, salicylic acid and a large number of oligopeptides. With the latter, it is relatively easy to understand whether they would be able to penetrate into the skin: most often, the number of amino-acids is indicated in the peptide’s name. You just need to learn to count in Greek. 🙂 Generally, di(2)-, tri(3)-, tetra(4)- and penta(5)-peptides are most often able to get through, hexa(6)-peptides usually can do the trick, while hepta(7)-, octa(8)-, nona(9)-peptides and further on would need extra help. I should probably note here, that growth factors, even though they are in fact peptides, don’t penetrate the skin easily because they are relatively large molecules.

Another thing is, when we are using the 500 Dalton Rule we generally suppose that the skin in question is healthy and undamaged. Imagine smooth and even skin, neither oily nor dry, without any scratches, pimples or uneven patches, perfectly beautiful at all times — in real life, not on a picture Photoshopped within an inch of its life. We all know how rare it is, because nearly all people have some skin concerns at one time or another, which is, by the way, completely normal. We can safely say here, that most skin concerns are connected with the damage to the skin’s protective barrier. Dry skin, for example, becomes thinner, loses moisture and has fewer lipids on its surface, thus leaving the door open for molecules larger than 500 Dalton.

(There is a lot of research on this, check this one for example, but most of them involve rather advanced math and are difficult to approach without special training.)

Oily skin in its turn suffers from diluted pores, and the mouths of sebaceous glands are open wide, like greasy little elevator shafts, allowing many molecules that wouldn’t normally be able to get into the skin to glide down right through.
We could also point out that the skin in different areas of the body and even the face has different permeability characteristics. It is easier to get under the skin around the eyes than, say, on the forehead.

However, even for the damaged skin there is a molecule weight limit where permeation is concerned — we are not talking about several thousand Dalton large molecules here. Various enormous polysaccharides, such as native hyaluronic acid molecule, will inevitably remain right on the skin surface, unable to get in, as plenty of research data confirms.

Lipophilic (fat-soluble) substance penetrate the skin easier, hence the popular trend in cosmetic chemistry to attach lipophilic “tails” to water-soluble molecules. Often these tails are the remains of fatty acids — when you see “palmitoyl” in a peptide’s name, that’s exactly what it is. Palmitoyl attached to NH2 group of a peptide allows it to dive and soak through the epidermis cells. The extra advantage of this method is, that while such peptide is able to get into the dermis, your body will stop it into getting inside the blood vessels, thus eliminating the risk of systemic effect.

Besides, we can change the skin’s diffusion ability and achieve a deeper penetration of some larger molecules.
There are two ways to do that:

  1. Without damaging the keratinous layer’s barrier simply apply a very concentrated solution, hoping that some molecules will be able to make it through. This sounds a bit silly, but it actually works well for very active substances, when even a tiny amount that does penetrate actually makes a difference.
  2. Damage the barrier with some chemical or mechanical agent, then apply your solution and achieve its penetration while the skin is healing the injury.

There are many ways to damage the skin’s barrier, both physically and chemically. The choices are overwhelming. We’ve got iontophoresis (works with ionised solutions), sonophoresis (the use of ultrasound, the substance is injected into the contact gel), thermophoresis (raising the temperature locally and diluting the capillaries) and magnetophoresis (applying magnets). The latter two, I would venture to say, have yet to be proven effective at all, but many practicing cosmetologists favour them and use actively. Of course, there’s always laser, most often it would be fractional laser “burning” micro-channels in the skin: if good stuff has been applied onto the skin prior to laser attack, it’ll have a chance to penetrate through, given that this substance is suitable for this kind of therapy. Radio frequency therapy is based upon a similar principle. There are machines that apply substances on the skin under pressure: they take water solutions of low-molecular weight ingredients and basically blow them hard into the skin for local effect, I kid you not.

As for the chemical methods, today there are over 300 ingredients commonly known as penetration enhancers. (Follow this link for a good article (pdf) on that.)
Chemical enhancers are used more often and considered more promising compared to physical methods: no need to invest in machines, no complications or contraindications, and most importantly, with chemical enhancers you can produce skincare solutions for daily use at home.

(Generally, if you’re choosing between a professional skin treatment that you can have once or several times a year and a routine use of quality skincare, my advice would be — go for the latter. Your skin will respond best to the regularity and consistency of care and will thank you for that.)

So what chemical enhancers do we know?

Quite unexpectedly, one of the most efficient chemical enhancers is water. Water itself is a transport for active substances in the skin. An important factor in the skin’s permeability is the moisture level of the keratinous layer. Normally the keratinous layer is only partially moisturised, water making up about 30% of its total mass in the healthy skin, but if we enhance water gradient (the ratio of water to dry tissue) we’ll increase the permeability of the keratinous layer several times. This way we can increase the skin’s permeability for water-soluble polarised substances, or to put it simply, this is how our sheet masks work: they are soaked in active gel and applied on the skin covered with water-soluble product with active polar molecules. After the mask is removed, the keratinous layer dries returning back to its normal permeability — which is how we want it to stay anyway.

Another widely used method is adding various hydrocarbon compounds: alkanes, alkynes, mineral oil, squalane, squalene and others. They destroy the structure of bi-lipid layer in the keratinous layer of the epidermis enhancing penetration of some molecules into the skin. This is a more complex way, because none of these compounds are universal enhancers, they are only able to facilitate the penetration of some molecules, not just any given one. For example, mineral oil eases methyl nicotinate and other forms of niacin into the skin, while caffeine would not be helped by it at all, relying instead on alkanes with short carbon chains.

Alcohols are used to enhance penetration too, although certainly not ethanol. Most often cosmetics use glycols, polyglycols, glycerol and alkanols. Their effect is quite varied: they destroy the structures of the keratinous layer, increase water gradient and enhance the solubility of an active ingredient. Their main drawback is that they are able to damage the skin’s barrier function for longer time than we’d like and with regular use they can cause skin irritation very easily.

Fatty acids are also of interest where skin’s permeability is concerned, most well-known of them being oleic acid, derived from olive oil. Olive oil in itself is a kind of locomotive splitting the fats of the keratinous layer and pulling into the skin whatever had been added to it, for example, caffeine combined with olive oil makes an effective anti-cellulite solution.

I won’t name all the possibilities, of course, I’m afraid very few readers have stayed with me thus far as it is, but I’ll add a few more. There is also urea (and other amides), isopropyl myristate (and other ethers), various surface-active substances (they irritate the skin, so not such a great idea), terpenes and terpenoids (essential oils are rich in those and in the composition of a cosmetic cream they help its active ingredients penetrate deeper). The smaller a terpene’s molecule is, the wider path it opens for everything else; the smallest terpenes are found in bergamot, juniper and some citrus essential oils, but they are also the most irritating for the skin and increase its sensitivity to UV damage. Another commonly used enhancing ingredient is dimethyl sulfoxide, described as early as 1964. We still don’t understand its effect in its entirety, but we know that it substitutes the bound water molecules in the keratinous layer.
Generally, there is plenty of room for using enhancers, developing new ones and combining them in many creative ways.

As you see, the skin itself is, in fact, permeable and getting active ingredients into its deeper layers is not impossible at all. Note, that the price of your day cream does not indicate how deep it is able to penetrate into your skin at all.

In truth, today’s legislation for cosmetic manufacture in most countries does not allow to sell any cosmetic product able to penetrate deeper than the uppermost surface level of the skin. Which brings us to a much more urgent problem of cosmetic development — how to retain the active ingredients in the keratinous layer. A lot of stuff that doesn’t go deeper than that is actually great for your skin and in most cases quite enough, too. But whether or not driving active ingredients deeper into your skin is justified at all, is another story for some other time.

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