Skin Penetration Enhancers – Friend Or Foe

Are We Dealing With Friend Or Foe In Skincare Ingredients?

Along with all the other misnomers and hype we have to wade through, including marketing, put out there about cosmetic ingredients, good or bad, watchdog groups also want to muddy ones’ thinking by making claims that penetration enhancers utilized in cosmetics and skincare are spreading poisons into our bodies at an alarming rate. But let’s not get carried away from the actual science here, or allow emotive jargon to cloud our judgment.

All of this theory and supposition, I guess, is going to be based on ones own perspective of the science. Personally, after reviewing the science on penetration enhancers, I believe they are a good thing in relation to pharmaceutical and skincare performance since our skin acts as an impermeable barrier to anything that comes in contact with it. Skin creams used for fighting free radicals and the aging process would be worthless if we can’t go any deeper than the immediate surface of the skin. Antioxidants, Herbal Extracts and Essential Oils couldn’t perform of what they are intended without penetration enhancers, in fact some EO’s are in and of themselves penetration enhancers.

Now remember, when we refer to penetration enhancers we are not discussing a delivery system of toxic ingredients like arsenic, strychnine, or supposed endocrine disruptors, or anything which we would remotely be considered poisonous to our bodies or what the EWG and skin deep database would wish to convey as such. The use of some penetration enhancers are also combined with nano particles in order to reach deeper within our bodies such as delivery of medications requiring them to reach the blood brain barrier, penetrating not only the stratum corneum and the epidermis, but also into and beyond the dermis layer. In the studies which follow we will look at the delivery systems and the benefits for their use.

Let’s Peek At The Actual Science

PubMed excerpt makes this correlation in part:

“One long-standing approach for improving transdermal drug delivery uses penetration enhancers (also called sorption promoters or accelerants) which penetrate into skin to reversibly decrease the barrier resistance. Many potential sites and modes of action have been identified for skin penetration enhancers; the intercellular lipid matrix in which the accelerants may disrupt the packing motif, the intracellular keratin domains or through increasing drug partitioning into the tissue by acting as a solvent for the permeant within the membrane.”

A more recent PubMed article concurs with further research:

“Novel techniques for drug delivery have been investigated in human medicine in recent years. The transdermal route of drug delivery has attracted researchers due to many biomedical advantages associated with it. However, excellent impervious nature of skin is the greatest challenge that has to be overcome for successfully delivering drug molecules to the systemic circulation by this route. One long-standing approach for improving transdermal drug delivery uses penetration enhancers (also called sorption promoters or accelerants) that can reversibly compromise the skin’s barrier function and consequently allow the entry of otherwise poorly penetrating molecules into the membrane and through to the systemic circulation. A large number of fatty acids have been used as permeation enhancers. They have proven to be effective and safe sorption promoters. This present review includes the classification, feasibility and application of fatty acids as sorption promoters for improved delivery of drug through skin.”

The problem is EWG and CFSC are among those that wish to label all penetration enhancers as “BAD”, instead of separation of the proven science in support of their use for the safety and efficacy they provide the user. The critical analysis here is, if personal care products could do all the things many marketing claims state they could do, then women wouldn’t be injecting Botox or Restylane. Which basically means, that if penetration of actual skincare products was any deeper than the actual dermis, then injections wouldn’t even be necessary.

No, Not My Olive Oil

I just recently learned that the EU is now looking at Olive Oil as a penetration enhancer and may be making a determination on its’ restricted use in products made for small children….I believe 6 and under was the targeted age group, but I don’t currently have the parameters of the restrictions the skincare companies may be faced with.

Olive Oil is a fatty acid which has been shown to have promising results in this field of study, though limited compared to others in penetration enhancement. What I found interesting in doing more research is, in a study performed in 2007 using in vivo, they determined human skin is usually the preferred skin membrance to use in an absorption study. No animal model gives absorption values identical to those obtained in human skin. Something I have tried repeatedly to convey in past articles that animal studies will not and cannot extrapolate to human beings as much as EWG, CFSC and their skin deep database would love them to, nor can in vitro (petri dish) compare to contact with actual human skin. The stratum corneum has long been considered a major barrier to the penetration of topically applied chemicals despite what ideologues try to pressure others into believing without supporting evidence.

The effects studied are shown with four essential oils (rosemary, ylang, lilacin, and peppermint oils), and three plant oils( jojoba oil, corn germ oil, and olive oil) on the permeation of human skin. These oils were compared with three synthetic chemical penetration enhancers, one of which is ethanol, and though the penetration of the oils enhanced permeation, their effects were less than the ethanol.

Aminophylline was the ingredient in this particular study for enhancing its absorption into the skin.

What I found interesting on page 6, in figure 3 of the study, and in the synopsis of the Journal of Cosmetic Science, out of all the oils used, Olive Oil performed the least in permeation of the skin.

So I have to wonder what is the motivation for the EU to be concerned with this ingredient when Jojoba Oil appears to perform the best overall for enhancing penetration of other ingredients? Again this is the reason why jojoba oil is excellent for dissolving and controlling excess sebum and maintaining skins pH balance, and I personally love this wax ester for what benefits it offers to skin, including the fact it is rich in antioxidants.

EO’s also performed much better for enhanced absorption as a result of this study compared to Olive Oil.

I personally love Olive Oil and its’ anti-aging benefits for the body inside and out. I am not too concerned about its’ effective use in skincare as a penetration enhancer because that is exactly what I want it to do. I find it to be wonderful for soothing many skin irritations, and the fatty acid profile is exceptional for topical treatment of skin ailments since it acts as a natural steroid due to constituents of natural sterols, squalene and polyphenols, helping to calm many skin issues. Plus other studies in Asia showed that it was the preferred oil for baby massage over mineral oil since it is readily absorbed more easily, and offers more skin benefits for fighting irritation and dry skin in infants.

I also found this article written by International Association of Infant Massage (UK) Chapter very interesting in relation to all the oils used in infant massage and Olive Oil is among them for similarly what I described above. They may take issue with the EU restricting this luxurious oil or any other which may be deemed a penetration enhancer.

Let’s Look At Concurring Facts

Another Study was performed utilizing other fatty acids and ethanol determining the increased absorption and retention of cortisol within the skin.

This study was performed by Sherry Jung, Biological Sciences. She has been an HSEP Medical Volunteer, a Peer Educator for the Counseling Center, and has served as a Biological Sciences Representative on the ASUCI Legislative Council. She is also a founding member and the current editor-in-chief of Med Times.

“The current project by Sherry Jung has served to illuminate our understanding of the penetration of a common dermatological drug when used in combination with a custom synthesized polymer. The results obtained point to direct applications in the field of dermatology as the polymeric compounds may be further modified for targeted-drug delivery. The avenues of research in this area are numerous, and we anticipate ongoing investigations using novel polymeric penetration enhancers.”

In one portion of the discussion as determined during the study, the skin structure is composed of three resilient layers: stratum corneum, epidermis, and dermis. The amalgamation of these transitional layers and their physical properties and physiological forces designates the skin as an ideal component in regulating absorption and retention. Absorption and retention are dependent on many factors, including pH, molecular weight, solubility, electrolytes, polarity, and especially the lipophilic/hydrophilic nature of the molecules involved. Furthermore, the effectiveness of topically applied therapeutic drugs is dependent upon the retention in skin layers and the transdermal absorption into specific target tissues.

Critical Thinking Versus Being Scared

Many ingredients’ molecular structure are simply too large to otherwise penetrate the outer layer of our skin, so without fatty acids or a synthetic penetration enhancer, depending on your preference, a simple, basic skin cream will essentially just sit on top and do nothing but soften and create an additional barrier for preventing dehydration of the skin.

Furthermore, with all the research I have combed over in past few years including these latest studies above, molecular size of ingredients prevent most cosmetic and skincare products from going beneath the immediate skins surface without help to achieve penetration of the stratum corneum. Penetration enhancers are utilized to provide the deliverance of essential skincare ingredients which can have a cumulative or immediate short term effect on improving skin texture and it’s appearance while using the product.

But what we really should be looking at, are these penetration enhancers carrying any other ingredients of concern into the blood brain barrier?…..the likelihood is slim based on the evidence of nano scale size particles being required in many instances to even come close to reaching the blood brain barrier. And in past articles, such as what was in the EPA Report, even this particle size will find great difficulty permeating healthy skin without a penetration enhancer acting as a catalyst. The diagram (left) simulates the depth of skin layers and conveys in relation of the surface of our skin to the blood vessels and lymph nodes.

I could not find a single study that actually determined the penetration of the blood brain barrier with cosmetic ingredients utilizing penetration enhancers, only the scare mongering and supposition perpetuated by EWG and CFSC without any peer reviewed studies to substantiate their claims.

Only those of pharmaceutical origin, which is exactly the purpose of penetration enhancers and nano science, were shown to be beneficial in this context of delivery of therapeutic drugs, but certainly should not be used to draw a conclusion that this extrapolates to cosmetics or skincare.

This is another scare tactic being used to take something positive within the medical field and twist it to the negative for self serving goals, by trying to convince the public that these same penetration enhancers are carrying everything we place on our skin right into our circulatory system. And if this can be done on a medical patch it must somehow do the same within cosmetic and skincare formulations…..

Cosmetics and skincare are not generally associated with big pharma, nor are they medicines, so their structure is for the purposes of treating the surface layers of our skin temporarily and should not be correlated as one in the same with a pharmaceutical delivery of medication through patches requiring a systemic effect. Because if they could perform as such, then they would require FDA approval and would be marketed as a “drug.”

When it comes to skincare, I want my products to perform beyond simply just sitting on top of my skin. If an additional benefit of delivery of any essential anti-aging ingredient (antioxidants or Retinol) can be enhanced into reaching the epidermis, including softening and reducing fine lines and wrinkles, and sustain hydration of the skin, then that’s the one for me.

It still is personal choice…..if you think penetration enhancers in skincare are doing far more to your body than treating surface layers of the skin, then by all means be wary, but remember, penetration enhancement is also not black and white….as it showed in the studies above, in some cases it requires a combination of ingredients and the perfect chemistry to achieve exemplary penetration of what the research was trying to achieve (therapeutic drugs), and the molecular structure of the ingredient being enhanced also plays a role.

As shown in these studies, natural chemicals also are penetration enhancers, so even with the use of an all natural skincare or cosmetic product, you will not be able to avoid these in any way, shape or form. Another reason to remember to take what the EWG and CFSC and their skin deep database state with a grain of salt, because frankly, they can’t have it both ways….. and sadly this fact seems to be lost entirely on much of the all natural, certified organic skincare community.

This is where critical thinking and a touch of common sense should be used, but alas, as I see in so many forums or blogs on these subjects, are usually prefaced with a firm belief based on an ideology, whereby ignoring the actual science when it doesn’t suit an agenda they are pursuing. It is especially disconcerting when skin deep database simply places scores of hazard without the balance of actual risk to the consumer, or EVEN references an ingredient in such a manner when they have 100% data gaps….their clairvoyance of such things is mind boggling.

The fact is, eliminate (ban) penetration enhancers based on ridiculous theories void of all science or the (beneficial) constituents these same ingredients may possess, and the majority of your natural skincare products (including my own formulations) will disappear from the store shelves as well as their synthetically derived counterparts. Now that would be a travesty!

But hey, there’s always Vaseline and water!

  • Dene Godfrey

    Hi Katie, just by way of clarification regarding the olive oil penetration (as I think you have taken this from one of my comments on another post), it is NOT the EU that are looking at banning the use of olive oil in products intended for use on infants, it is a group of dermatologists in the UK who have expressed their concerns – no more than this at present. Also, these concerns are NOT over olive oil, per se, and I doubt they would have any issues with the use of pure olive oil used in massage. The issue they DO have is that, when incorporated into cosmetics, olive oil has the potential to carry other substances within those cosmetics through the skin that would otherwise remain on the surface. Given the extra sensitivity of the skin of infants, this increases the potential for adverse effects, but will depend entirely upon the other ingredients, of course. There is no suggestion that olive oil should be banned in general terms, and no suggestion that it is not, in itself, safe to use.

    • Philippe Papadimitriou

      I have not heard of anything about an olive oil restriction, but would like to inform readers that young age categories are made as such in the EU (targeted population to be specified on safety assessment):
      – babies 7 years

      Other classes are:
      – adults (= or > 18 years)
      – pregnant women
      – professional (specify)
      – other (specify)

      It is not impossible that this present classification will be kept in addition to some weight classes next to it in the future.

      PS: Olive oil is very interesting as its fatty acids composition is very similar to human skin’s.

    • Katherine

      Hi Dene,

      Thanks for clarifying my mistake, I’ll definitely want to correct his error within my blog article, and I’ll make a followup to this correction in this weeks blog. So happy to know that they will only be looking at this in the context of “in combination” of other ingredients. However it still puzzles me why they would be concerned about “olive oil” when it is shown to not have as good penetrating ability as other oils like EO’s or Jojoba Oil. And these were just the ones I found studies on. I don’t know how it stands against other fatty acids for penetrating the skin in terms of further studies.

      Again though thanks for correcting my faux pas.

      • Dene62

        Hi Katie,

        No problem. I have no idea what the current status of the project is, nor if they are looking at any other specific ingredients. Nothing may come of this, but it was clear from the dermatologist giving the presentation that olive oil was of concern to him and his colleagues. I am not trying to cause a scare; just passing on genuine information! It has not been widely publicised, so I am not surprised that you were not aware of this.

  • Arlene Chase

    Critical thinking? Our government is trying to out law it by doing our thinking for us!!

  • Philippe Papadimitriou

    Dear Katherine,

    This is a good article and I would thank you for having taken time to cover this issue further.

    Skin is an incredible barrier and the stratum corneum is a difficult step to pass for many different agents, being chemical, physical or biological ones. But even if skin is one of the most fantastic barriers, it isn’t at all fully impermeable. Many classes and types of molecules have been shown to enter skin, whether we want it or not. Everything depends on nature, size, charge, Kp, etc. The good news is that among the thousands of millions of molecules, only a small minority may enter (they are then variously metabolized in the epidermis, dermis, liver, kidneys or excreted). The portion (of the applied dose) penetrating will rarely be important and the penetration rate (i.e. speed) is also mediocre in general, even for these “lucky chosen” substances. Glycerol, some steroids, fatty acids, nicotine and nicotinates are a few examples of substances that penetrate human skin.
    The reason why pharmaceutical patches exist is because the molecules delivered through these devices may cross the cutaneous barrier. But patches do not exist for all susbtances and this is the reason why topically applied balms, creams and lotions still exist even for pharmaceuticals (!). The concept of produg (a molecule metabiolized as a first step in the human body to become the active substance that is actually the drug) is not used in patches to my knowledge for the reason skin is too good a barrier in general.

    The whole concept of “penetration enhancement” is based on how to permit more important a penetration for a substance that originally only displays a poor or limited penetration (rate, depth or amount) in human skin because of its chemical structure and nature. This may be achieved with the use of molecules showing a great affinity to skin AND (read: simultaneously) the molecule(s) targeted for entry!!!
    -> It is not because a penetration enhancer is present that the whole formula (with emulsifiers, preservatives, etc.) will penetrate, no!! I think it was important to add this.
    Fatty acids contained in vegetable oils will thus not enhance the penetration of very hydrophilic peptides, for example, but may help some specific oily components to be better delivered.

    Penetration enhancers might be chemical agents, like fats (the case of olive oil, or fatty acids), solvents (glycols, alcool, etc. or the right mixture of solvents), but also emulsifiers (sucrose esters, for example, or other more complex 3D delivery systems (liposomes, nanospheres, microcapsules, microspheres, ethosomes, etc.). Some molecules will also adsorb on particules for an enhanced penetration (see for a good start). Other ways to enhance penetration are i) to formulate stable multiple emulsions, ii) to use cationic silicone complexes or even iii) enzymatically activated encapsulation techniques. Every strategy has its limitations (affinity/size/…) and its obstacles (formulation/incompatibilities/…), not to mention its price. Physical techniques exist too, but they are by now only used in the pharma industry or in fundamental research (see, for example).

    As one sees, skin delivery is far more complex and complicated that it often seems, but also far more studied than some would let us think it is. Topical application has its limits, but a safe reversible disruption of the skin barrier and other milder methods exist for the enhanced penetration of a desired substance. The price of such techniques is very often the limitant step for cosmetic manufacturers and in consequence only major actors tend to take advantage of them, but with all safety measures strictly taken as efficacy based on deliverability is definitely linked to safety.
    The concept of safety assessment in the EU helps to frame further this safety aspect as responsible toxicologists and safety assessors need to closely follow the litterature concerning delivery systems and ask more about formulations to the manufacturers.

    NB: Whatever the penetration enhancement or delivery system used, some molecules will still NEVER penetrate and this accounts for the resort of sub cutaneous injections of drugs or susbtances like those used in medical aesthetics (botox, hyaluronic acid,..).

    As I hope many have now percieved and/or understood, penetration enhancement may not only be seen in INCI designations. It is not because a penetration enhancer has an INCI name declared on the packaging that the formula containing it will have some form of added penetration (and if it does, it won’t help the whole formula to penetrate, but only a very limited part of it). Some formula with apparently no delivery system will nonetheless penetrate better than other because of the formulation art behind. Some other may finally contain empty liposomes added for marketing impact (but nothing to deliver – a supplier told me about this case; the delivery system was Ecocert approved so it was “cool” to seem and natural and technological..).

    An INCI list will never teach the lambda consumer if any penetration system was used (deliberately or not!) and having any form of restriction, ban or bad grades attributed on a substance known for its penetration enhancer properties will ultimately be some stupid idea.
    What about water, then?

    I am sorry, I know of no “Chemistry for dummies” book addressing the issue.

    Recommended general bibliography on delivery systems:

    Delivery System Handbook for the Personal Care and Cosmetic Products. Technology, Applications, and Formulations, MR Rosen, ed, Norwich, New York, USA: William Andrew, Inc (2005)

    All publications of expert and pioneer Johann Wiechers

    • Katherinecorkill

      Hi Philippe,

      Needless to say your followup would definitely make for another article taking it to the next level of a better and continuing understanding of skin penetration enhancers.

      In fact my article does make the point, however, maybe not directly about not all ingredients will not penetrate the skins surface. I did use the terminology of “essential” anti-aging ingredients, rather than breaking it down to those that would not penetrate such as emulsifiers and preservatives. It is still about the penetration to the circulatory system that may have some concerned, and in most cases even those wanting the important ingredients to penetrate will only go so far.

      I also did make the correlation to penetration in regard to the chemical engineering to make this happen and was emphasized in bold.

      All the additional points you make are excellent, are certainly needing to be further understood in the context of how this is perceived by the EWG and CFSC, and they are much more elaborate to my simpler article with links to the studies showing how this is done. And though I do not have the extensive scientific background as other experts on here, I also write for my readers of my blog and I will provide the science as often as necessary, but you will find my articles to be written in an easy to understand context, leaving the actual more involved studies within the links provided if my readers should so choose to research further.

      But your response is truly appropriate for PCT and I thank you for expanding on the finer points of my article. The more information we can provide to those that follow PCT the better.

      Thank you

      • Philippe Papadimitriou

        Hello Katherine,

        Your article was excellent. It was not my intention to develop the same aspects of skin penetration in my comment. I agree with you most of what I have written could have been used for another article per se. My idea was to also consider the cosmetic scientists’ readership of PCT as I hope they are also the readers of this site.

        I have the feeling that in the penetration debate, most experts of “our” side chose to argue so as to pretend that nothing penetrates to not let our opponent use the break (I am not addressing this to you – this is a general finding). This is PCT and we have to admit some things penetrate and some other are absorbed via the skin (the case of nicotine). This is known and obviously considered when ingredients are designed or selected for an acceptable use in comsetic products.
        My point was to show with explicit examples that the skin is definitely not porous, but not made of stainless steal either. These examples cover the parameters you quoted (patches, sub cutaneous injections) to put them in perspective in the eyes of some who do not make the difference. They were given to exactly demonstrate that some substances do penetrate, but only some.

        Skin delivery tactics and penetration enhancers are not used for all ingredients present in one formula to penetrate better. They are used as strategies for one of two particularly safe selected ingredient(s) to reach their target. Their target is never the blood or lymph system, of course.

        (Accept my apologies if I do not only answer to you with this additional comment – I also further or again develop points addressed above).

        Your articles are always fine and I like to comment on them. Keep on doing good work!

        • Katherine

          Thanks Philippe,

          I get where you are coming from and I always appreciate your input. I also apologize if some of my comment above is a bit muddled, I just returned from the Natural Products Expo in Anaheim and I am not 100% yet. I couldn’t even figure out how to sign in as me instead of a guest! All fixed now!

          Please also know that clarification of science is always essential and this I’ll never dispute. I do try to keep it simple at best and save the intense write ups for the true science experts.