Let’s Talk Penetration


PLOT SPOILER ALERT!  There is a “dirty little secret” in the skin care biz. I’m about to spill the beans. Click your back button if you have a weak stomach or if there are children in the room (in case you let out an expletive). Ready? Here it is.

Most of the “actives” you put on your skin never get absorbed to the layer of the skin where they are supposed to act.

OMG! You mean those very expensive little molecules are just sitting there on the surface? Then washed away, down the drain?

The answer is yes.

Now, in recent years, some in the biz have confessed this secret, and have set about to solve the problem with technology. Studies of new methods of penetration augmentation are gaining experimental and clinical interest. Penetration enhancers are a hot topic in derm science. Let’s “drill down” to find out why.

The skin’s natural barrier to outside stuff – necessary to life as we know it

Let’s talk for a minute about the skins barrier to entry – the stratum corneum. It’s a very good thing – keeps us alive by protecting us from all the nasties of the world. The outermost layer of skin cells, or “horny layer”.  It has a very peculiar structure: the corneocytes (the bricks made of “dead” cells: about 85% of the mass of horny mass) and intercellular lipids (15%) are arranged in approximately 15-20 layers. It consists of about 70 percent proteins, 15 percent lipids, and only 15 percent water.

The corneocyte bricks are poor in lipids, but rich in proteins. The lipids are outside the corneocytes, like mortar for the bricks.  The very low permeability of the horny layer to water soluble substances is because of these lipids—while penetration of fat soluble substances is limited by a convoluted and tortuous intercellular space. Size matters. Larger molecules are disadvantaged. If fact, we sometimes talk about a “500 Dalton rule”. Molecules heftier than 500 Daltons  (which is very tiny indeed) have very low penetration without assistance.  Most actives are polar, and weight in well beyond the 500 D limit.  Successful penetration through the stratum corneum involves a partitioning between hydrophilic (water loving) and lipophilic (fat loving) compartments. More on this below.

Water & chemicals

Many things affect absorption. Hydration (water and things that carry it) is very potent. Corneocytes swell and the barrier properties of the stratum corneum are deeply altered. The effect of the hydration however depends on the active – some are greatly amplified, others barely at all.  There are chemical enhancers that alter the lipid part of the barrier. Some of these degrade the natural skin lipids, and can leave skin feeling dry and make it susceptible to irritation. Rubbing alcohol is an extreme example. Most chemical penetrants have some risk as irritants. Oil/water emulsions are used as penetration enhancers. Emulsifiers may be the commonest strategy used. But the magnitude of their effect is limited.

Liposomes and Nanosomes

Liposomes take molecules your skin recognizes as foreign and camouflages them so that they look like friendlies.  They are composed of natural phospholipids, molecules with water soluble heads and fat soluble tails. They are constituted as envelopes which surround molecules of dermal actives. Liposomes can carry both hydrophobic molecules and hydrophilic molecules, disguising their polarity, and giving them hall passes through the stratum corneum. Nanosomes are like liposomes, but smaller (between 10 to 1000 nanometers) giving them a size advantage. They may have a solid lipid core matrix that in which they can carry lipophilic molecules, stabilized by a surfactant. Many different types of physiological (natural to the body) lipids can be used, limiting toxicity.  They are generally more stable than liposomes, which have a shorter half-life in a finished skin care product.  Nanoparticles also can create a “controlled occlusion” which also enhances penetration.

Physical Enhancers

You can also beat the defenses of the stratum corneum by punching holes in it (dermarolling, fractal lasers), vibrating it with ultrasound waves, applying electrical currents (iontophoresis), and even magnets. These can be tricky because they involve devices (from simple to complex) with parameters than need to be set correctly to improve penetration. For instance with dermarollers, you can alter needle size to reach different layers of the epidermis, or even drive actives directly into the dermis. You want to be sure that actives you use with these are supposed to be in the dermis, otherwise you can induce a toxic or immunologic reaction, leading to scar tissue formation.

Bottom Line

Nobody wants to spend hard earned cash on products with actives that never get to where they can act. Which is why you rarely hear about this topic. Most products simply ignore it, their purveyors hoping you won’t ask questions. We encourage you to do just that – ask questions.  In online forums, at the point of purchase, or write them an e-mail – “tell me how <active x> gets to where you say it works. “  If they tell you “we don’t know”, or make up some malarkey about its magical properties that defy known chemistry and physics, you might want to think twice about that purchase.

The stratum corneum does an amazing job of protecting us. If we are going to override that, let’s make sure we are doing so carefully and thoughtfully.  If you see liposomes or nanoparticles or some other penetration technology, or plan to apply some product after a dermaroll, then ask “is it OK for that stuff to get way deep into my skin?” If it is not natural (to humans, which excludes a lot of botanical chemicals), or not tested for safety by that mode of entry, the answer could be no.  If the active molecule  is a man-made invention (it should be called a drug, but some skin care companies ignore that), then I would ask for adequate toxicologic and safety data before allowing that penetration to take place.


  1. G says:


    Many serums feature very high concentrations of alcohol – in Ultraceuticals Red Action Complex it is the 2nd ingredient. What is your opinion on using alcohol as a penetration enhancer? Does it cause inflammation that outweighs the benefits of the actives it delivers to skin?

    • drjohn says:

      Depends on how high. Mostly you see only tiny amounts of alcohol, usually in the formula as a tagalong from some ingredients that used alcohol as a surfactant or emulsifier. In that context it doesn’t cause problems, and won’t be inflammatory, unless there in high concentrations. But it is odd that they would put so much ethanol in there. Maybe it’s 98% water, 1% ethanol, and the other ingredients are sprinkled on. Maybe they are swimming in industrial (tax free) ethanol and the product is just an excuse to buy another barrel for a martini party!

  2. ChicGeek says:

    You forgot two. Micro and nanoemulsins and also chemical penetration enhancers, both those that disrupt the lipid barrier and those that slide past.

    • drjohn says:

      That was a 2012 post. Since then we started up our own nanotechnology lab, which has spun off as Nanostrips, Inc. We need to do an update – much has been discovered about skin penetration in the past several years.

  3. Megs says:

    What should I put on my skin after dermarolling?

    • drgeorge says:

      Megs, BFT has answered many questions about microneedling (same thing as dermarolling). May we ask you to do some searching around using key words or comment strings. Our biggest concern is that most people using microneedling are not aware that the barrier function of the skin is greatly reduced for the first several hours after treatment. The skin is very susceptible to foreign substances during this time, particularly ones with non-physiologic ingredients. Nasty reactions can occur.

      Our recommendations (because we formulate and produce them, we know that all ingredients are physiologic and safe) are AnteAGE MD, AnteAGE, and AnteAGE HOME versions of Microneedling solution. You can contact us if you want to learn how to obtain them.

Leave a Comment