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Understanding Transdermal Delivery with Amie Skilton

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Understanding Transdermal Delivery with Amie Skilton

There is a growing clinical demand to deliver certain nutrients and compounds in transdermal preparations. One FX Medicine listener reached out to us, and asked us to explore transdermal delivery more deeply. So we enlisted the help of Amie Skilton, a naturopath, herbalist and aesthetician to talk about the finer details of delivering therapeutics via the skin.

In today's podcast Amie talks about the many variants in skin structure, integrity and hydration that can have an impact on the penetration of nutrients into the skin's deeper layers. She shares what forms of nutrients are most ideal for skin care and some salient cautions and contraindications to be mindful of. Amie also talks about barriers to research and why probiotic-fermented ingredients might be an important player in skin health in the future.      

Covered in this episode:

[00:38] Welcoming back Amie Skilton
[01:43] Examples of transdermal applications
[03:56] Overcoming the skin's barrier system
[06:07] Well known examples: Vitamin A and analogues
[08:12] Site of application impacts absorbability
[09:40] What clinical situations may call for topical therapies?
[12:13] What factors influence skin absorption?
[17:50] Nutraceuticals and cosmeceuticals
[20:50] Be cognizant of safety
[25:04] Future watch: Probiotic-fermented ingredients
[28:12] Optimising skin transdermal delivery
[35:11] Why there's mixed evidence on skin bioavailability
[38:45] What makes liposomes a great choice for transdermal?
[40:21] Wrap up and final thanks to Amie 

Andrew: This is FX Medicine, I'm Andrew Whitfield-Cook. Joining us in the studio today is Amie Skilton. She's a qualified naturopath, nutritionist, medical herbalist, and aesthetician. She's been in a clinical practice for more than 17 years and worked concurrently for the BioCeutical's technical team for 14 years as a presenter, educator, and writer.  
She specialises in several areas of integrative medicine, including women's health and hormones, natural fertility and healthy child development, gut restoration, as well as her favorite subject; skin health. 

Author of the book Clear Skin Secrets, Amie's truly a holistic skin specialist who helps women and men struggling with acne achieve healthy, clear, beautiful skin, naturally. Amie is the founder of whatthenaturopathsaid.com and theclearskincoach.com. You can also connect with her on Facebook, Twitter, and LinkedIn. Welcome warmly back to FX Medicine, Amie. 
Amie: Thank you, Andrew. 
Andrew: Now, we're going to be discussing something which I've got to say I know nothing about, transdermal nutrient absorption. Now, my experience of drug absorption is a little bit humorous. In the olden days, we didn't have these set-dose patches that we have nowadays for cardiac, certain cardiac drugs. In the olden days, in ICU, we used to have people on Nitro-Bid ointment, which was basically, you squeezed out a toothpaste length on a bit of grease paper, like baking paper, and it had a ruler.  
So the doctor used a write on “Nitro-Bid ointment 1.5 centimeters”. Inevitably, what would happen is that you’d get a little of an Nitro-Bid ointment on my skin. And then, of course, I was a smoker in those days, and this is in Wagga Wagga in winter. So we'd go outside and have a cigarette in the cold and almost drop from the vasodilatory effects of Nitro-Bid ointment. So I'm going to gather that what you're going to be talking about today is just a little bit different. 
Amie: Hmm, fractionally. 
Andrew: Let's talk about that. I have to say it seems weird. Tell me more about this. 
Amie: So in terms of transdermal absorption, there's a lot sort of out in the ether if you like, around how effective it is. If you look at the FDA. in terms of transdermal absorption of anything, their belief system is that it's negligible, which really does fly in the face of what we understand as far as drug delivery goes. And then on the other side of the coin, you also have well-meaning and well-intentioned natural skincare and natural health proponents suggesting that anything you put on your skin is… you absorb up to 65% of it, and in under 30 seconds you'll find it circulating in your bloodstream. And where the truth lies actually really depends on a lot of factors, but it's most certainly somewhere in between. 

So, first of all, I want to make the distinction between penetration and absorption. So when it comes to the topical application of anything, you can enhance its ability to penetrate the skin, whereby it makes it to the deeper layers of the skin. Meaning it overcomes the stratum corneum, which is that top layer.  
Andrew: Yeah, which is your barrier, your dead barrier. 
Amie: Yeah. That's the primary part of the barrier. Then you've got absorption whereby whatever active ingredients you're trying to deliver to the body, whether that's medication, whether that's a nutrient, whether that's a herbal medicine, actually makes it through to the bloodstream and to distal sites, which is an entirely different thing. Unfortunately, those two terms are often used interchangeably, but they are not interchangeable in terms of what they really mean.  
So transdermal delivery systems, as you've already mentioned, have been used for some time for various drugs including hormones like Estradiol and testosterone, local anesthetics like lidocaine as well as contraception. And in certain cases, using methods that enhance delivery like ultrasonic for analgesia as well. 

So the biggest challenge we have regardless of what active you are trying to deliver is getting past the stratum corneum, which is like a cement layer. That provides almost the entire barrier function of the skin. And so, getting through that is the first challenge. However, as you go through the different layers of the skin into the dermal-epidermal junction there are areas which are more conducive to the diffusion of hydrophobic or lipophilic ingredients, and then it actually alternates. And so you've got to consider the delivery vehicle as well as many other factors in order to achieve what you want to achieve. And I guess that's really the question the practitioner has to ask themselves, A, what are you trying to achieve? And B, why are you doing it this way?  
So when it comes to skin penetration, if you're trying to treat local skin conditions, that's all you need. And in that case, you may not have to be so concerned with the full absorption rate. Although when it comes to things like vitamin A, you probably want to be mindful of the absorption if you were say, using topical retinoids on a pregnant woman, for example. 
Andrew: But it would be very hard to get to the levels of, you know, we're now using retinol equivalents. 

Amie: Yes.

Andrew: It would be very hard to get to that... What is it? Either... no 10,000 I.U. at any stage of pregnancy regardless of vitamin A status. That was WHO working group on vitamin A. It'd be very hard to get to that level from topical delivery, wouldn't it? 
Amie: It would, although it does depend on many factors. It appears at this stage, if you look at studies based on tretinoin, with regards to liposomal delivery and topical application in acne vulgaris patients. It doesn't seem to raise the serum levels enough to be of concern. However, we do have to consider many factors, and in the case of, say, zinc deficiency or poor liver function or perhaps extensive vitamin A supplementation preconception, it would be something just to be mindful of. 
Andrew: I wonder if there's a pregnancy warning on, now what's it called, Stieva-A, I think it is? Is the trade name and it's a retinoid cream for acne. 
Amie: Yes, there are... as I understand it from what I've seen topical retinoids. 
Andrew: Another isotretinoin, like Roaccutane or Accutane overseas. 

Amie: Sure, yes. 

Andrew: I get that, and that's a black box warning for pregnancy. Yes, Stevia-A, topical? Got a warning? 
Amie: Even topical retinoids, yes, do have a warning. That's not to say that that contraindicated but it is something that needs to be professionally managed. 
Andrew: I think would rather be a litigious issue rather than a real issue but anyway. 
Amie: Definitely. And also it depends on where you're using it and why. So, for example, the site of application on the body does determine, amongst other factors, how much absorption actually occurs. 

So if you were to apply something to the forearm, the average absorption of that particular compound is around 8.5%. So and that what I mean by that is if you were to deliver a particular dose to the skin surface around 8.5% of those actives will make it all the way through to the bloodstream, assuming the delivery methodology has been considered, and other factors are all, sort of normalised.  
However, if it was to be applied to the scrotum, the skin on the scrotum has 100% absorption. And this is why for certain topically-applied drugs the recommendation is on the inner thigh or the inner upper arm because the skin tends to be thinner than on the outer edges of the limbs that are more exposed to the sun and consequently thicker. 
Andrew: Now that's really interesting you say that because I do remember an agricultural paper being circulated with regard to the percentage of absorption sites about around various areas of the body like they especially looked at eyes. They did mention scrotum, and they mentioned other sites of the body, with regards to pesticides and herbicides being absorbed.  
So obviously these things, or certain things can be absorbed, I guess not all. And, you know, I guess one of the issues floating around in my mind is we're obviously not talking about general nutrition. We're not talking about feeding the body through the skin, that's absurd. But just how real is this. And indeed, what sort of nutrients would you want to be absorbed rather than through the normal route? Why? Why bother? 
Amie: Well, generally speaking, certainly in the realm of complementary medicine, for the most part, topical application is going to be for the purposes of a local effect. 

Andrew: Yep.

Amie: So it's less so about attempting to deliver nutrients in a way other than that which we're normally accustomed to, which is gastrointestinally.  
However, if there are issues with high first pass metabolism in terms of medications. Whether that's herbal or pharmaceutical. Or there are issues with gastrointestinal sensitivities, inflammation, liver issues, and even renal issues, topical delivery can in some cases be desirable. And to give you one I suppose a practical example of that, I have a patient with SIBO, which we are on the way to eradicating. However, in the height of her condition, she was unable to consume fibre and any nutraceutical supplements just left her in gastrointestinal distress. And particularly, out of all of the nutrients, her body was crying out for she desperately needed magnesium. And up until that point, I had only ever successfully recommended oral delivery of magnesium using highly bioavailable form of amino acid chelate, and not had any issues with patients experiencing gastrointestinal distress.  
Unfortunately, even though I was using, in this case, one of the best forms of magnesium you can give, she still could not tolerate it, and yet was experiencing many of the symptoms we know our bodies will experience when our magnesium levels are low. So in this case, she began using a magnesium oil instead. And there is evidence to show that using topical magnesium can raise serum levels of magnesium as well. 
Andrew: You know you said a couple of interesting things earlier on there, and one of them was regarding first pass metabolism of the liver, and also trying to avoid side effects like gastrointestinal side effects of certain pharmaceuticals. What factors will affect absorption of these nutrients? 
Amie: I think there's a huge area of exploration here regarding the topical application of anything we put on our body quite frankly. Even seemingly benign chemicals generally regarded as safe, as well as nutrients and of course medications. 

But what makes it tricky is several fold. Firstly, when it comes to the study of toxicology, we know for the most part toxicology examines one chemical, one agent at a time, and doesn't account bio-individuality, and in addition to that, overlooks the synergism of combining multiple nutrients or chemicals for argument's sake.  
But really to give you an overview of the factors that influence the bioavailability and the absorbability of anything applied to the skin. And they really are... it's quite a lengthy list actually. First of all, how hydrated the skin is affects the absorption, and this is both internally and externally. So obviously healthy plump cells are a lot more able to respond to anything applied to them.  
However, water on the skin also softens some of that mortar between the bricks of the corneocytes allowing better penetration of the chemical or the nutrient. So anytime the skin is dehydrated, the absorption of anything applied to it will be slowed down, and particularly via the passive diffusion pathway. Which we'll talk about a little bit more in detail in a moment. 
The temperature of the skin, logically as you can probably imagine, the warmer it is, the better the circulation is to the surface of the skin, the easier it is for anything to cross over and be absorbed. Skin condition, of course, if there's any injury, or the skin barrier is compromised in any way, that gives the agent direct pathway straight into the deeper layers. And this can be used to our advantage in the case of microdermabrasion or micro needling when we're trying to heal the skin with, say, something like a vitamin C serum. 

I've touched on regional variability already, which is where certain areas of the skin provide really a greater barrier to penetration. So, for example, there are certain areas that can absorb nutrients or medicines more readily. We touched on the scrotum, certainly, the underarm is another one and anywhere that the skin is a bit thinner. 

Of course, individual variability plays into it as well, but then it comes down to what are the physical and chemical properties of the compound, what is the molecular weight, what is its polarity. The skin prefers lipophilic compounds, so it is easy to get fat-soluble agents and fat-soluble vitamins across than it is water soluble. But things like even carbon number and volatility play a role. 

The pH of the solution in which it is delivered is also key as is the fact that it's delivered in a solution. A diluted compound is often more able to penetrate the skin than if it is applied neat. And that's because the water actually softens the stratum corneum allowing greater diffusion. So that's quite an interesting one because that is slightly counterintuitive, you'd think applying, you know, a stronger more concentrated version of the product is a better idea. But the pH also affects the ability of the agent to cross the skin, and logically at the more extreme ends of acidity or alkalinity where it disrupts the hydrolipid film, allows for better diffusion across the skin. 

But beyond that, we can also employ other methodologies which will enhance delivery, and that includes the vehicle in which the agent is delivered in, and we'll talk about liposomes shortly. But anything that allows it to be delivered across those layers more readily is going to be supportive. And you can also use accelerants as well. And outside of, say, medical or clinical setting, this might be as simple as using a gentle glycolic acid peel on the face before applying, say, a serum to the skin for treatment. Or even alcohol disturbs the hydrolipid film of the skin. You can use ethanol to wipe the skin before actually applying a topical agent if you're trying to deliver something with a systemic effect for example. 
Andrew: And that would aid absorption rather than...? 
Amie: It does. 
Andrew: Okay. So what about with regards to blood flow because it evaporates and you get a temperature loss? 
Amie: You do, although in terms of where you're going to see the benefit, the disruption of the hydrolipid film is going to play a much more significant role in improving the delivery than any... 
Andrew: And I guess more immediate too, yeah. 
Amie: More immediate than any loss of initial local temperature, which can, of course, be overcome by manually rubbing in whatever you're applying. 
Andrew: Simple, keep it simple. They're really good points actually. And the more you speak about it, the more I think, well, you know, we already use this stuff for drug delivery. And within realms of, you know, the molecule size and active-passive transport that sort of stuff. There seems a logical argument for, you know, delivery. I don't know about dose, that would be an interesting one, but, you know, certainly local application. I mean, we've been doing it for decades. You know, CoQ10 in anti-aging creams. 
Amie: Yeah, absolutely. It's certainly in the field of cosmeceuticals. I think a lot more work has been done than in the field of sort of applying nutraceuticals in the same way. And I think partly because there hasn't been a huge need for it. Gastrointestinal delivery tends to work for most people. With advancements in technology we're able to manufacture nutraceutical compounds now with chelators that have fantastic bioavailability that overcome any gastrointestinal barriers that might cause upset. 

But when it comes to skin, I think much of the work has been done on the... really through the transcellular route through the stratum corneum.  
However, there is the appendages to consider, so you've got the sweat glands and the sebaceous glands, where you're actually going to have whatever you applied to the skin filter down through those and straight into the dermis, and also through the matrix layers via the intracellular route. And the pathways are not mutually exclusive either. But what I'm saying is I think there's a lot more understanding still to come with the way in which things can actually cross the skin barrier as well. 
Andrew: I think it's interesting though, you spoke about nutraceutical... Oh, sorry, cosmeceuticals. And there's even the use of herbs. Now, you know, let's face it, the cosmeceutical's agenda is for anti-aging, but when you think about it, let's talk about the application of cucumbers to the eyelids.  
Amie: Green tea. 
Andrew: Green tea. Tea bag on the eye... a steak on the eye for a bruising. I don't know how good that works for bruising. But with regards to, you know, mild swelling in oedema, it's been used and reused and reused. 
Amie: That's an exciting and emerging field, and I think there is a lot more to come here. And I think as we move into certain conditions or into cases of polypharmacy or individuals who are particularly sensitive, the trans-epidermal route is going to be one that I think is going to be really helpful for patients that find it difficult with taking anything orally. 
Andrew: But you have to obviously know about, you've mentioned quite a few factors and they're reasonable factors to consider. Especially things like skin types. You know, what's good for the gander might not be good for the goose. 
Amie: Correct. 
Andrew: So you've got to be really quite cognizant of that patient in that particular point of time and with their particular genetics and makeup. 
Amie: Yeah, absolutely. 
Andrew: What about safety issues then? The obvious one is burns, you know, but you're not going to be treating somebody with burns, that's a burns unit issue. 

Amie: Correct.

Andrew: You know, in nursing we've looked at this as an issue, not as an application, but as an issue. But what about in the clinic with naturopaths, do you find any safety concerns with nutraceuticals as opposed to pharmaceuticals? 
Amie: It does need to be put into context. When you consider pharmaceuticals, you have to understand you are introducing a foreign and synthetic agent into the body that has multiple consequences and considerations as far as elimination and metabolism and its pharmacological effects.  
If you are utilising vitamin C or vitamin A or magnesium or zinc, that is not in the same category as a pharmaceutical medication. However, all the same considerations as when you'd be orally administering those nutrients should be kept in mind. And so, knowing that fat-soluble nutrient delivery will be, in most cases, more effective than water-soluble nutrient delivery. You need to consider the impact of accumulation, and in vitamin A, I think it's probably the one to be most mindful of, especially if you are not giving zinc, which we know are is critical for vitamin A transport, release from the liver and delivery to the tissues. 

And so, I would simply treat them with the same respect as you would if you were delivering them orally. Knowing that the risk is a lot lower, but is currently undetermined. And in that way, you won't come unstuck. And so what I mean by that is if something is contraindicated in your patient to be delivered orally, I wouldn't therefore be applying it topically either. 
Andrew: But I do make that distinction of, you know, even vitamin A which we are a little bit paranoid about with regards to pregnancy, and I will put the IVAG Vitamin A paper and pregnancy up on the FX Medicine website for our listeners. But I do make that distinction between vitamin A and tretinoin, which is not vitamin A but a vitamin A analog. It's a drug that works differently. 
Amie: Sure. It is. It is. That is an important distinction to make certainly. But I guess another thing I would share in response to your question about safety is if, for example, someone has epilepsy and there are certain nutrients contraindicated in that condition, I wouldn't go and apply them topically either. Because it is currently not known what that delivery is like and whether you may be putting them at risk.  
And I guess the other thing that I would just keep in my mind is what the condition of the skin is like. Are they sensitive? Is it sensitised? If they have dehydrated, dry, or sensitive type skin, be very mindful about what excipients or delivery agents may be in what you're applying topically, as well as the potential for any of the actives to alter the condition of the skin and/or be potentially irritating. 

So like anything, I would recommend patch testing with a small dose first before applying something liberally because you can't take it back. 
Andrew: No. I'm thinking of applying B12 to my skin. Don't. Do. That.  
Amie: Please don't. 
Andrew: You’ll stain not just your skin but every part of your clothing as well. So obviously there's inappropriate nutrients, you know, you wouldn't consider for absorption, and the obvious one there is B12 because it stains the hell out of things. Curcumin. Despite the fact that I see curcumin face masks on YouTube. 
Amie: Yes, they are great if you like a Dorito glow.  
Andrew: But although what about, you like the face masks on YouTube, they clean up seemingly quite nicely. 
Amie: Yeah, they do. 
Andrew: I think that might be the base of this in those, is that right? 
Amie: Yeah, it could be and also how much you use and also how well you take it off, that's for sure. But there are ways that you can improve its delivery. And I want to just throw out there an area that I think is going to be one to watch, and that is probiotic-fermented ingredients. 
Andrew: Hang on, I'm not aware this. This is new. Please explain. 
Amie: Sure. So much has been elucidated around the benefits of probiotic bacteria and our commensal microorganisms. And some of the things that we understand that they do for us is liberate compounds from the things we eat, I'm talking on gastrointestinal here for a moment. 

To give you an example, everyone knows dark chocolate is good for us, and that is because of the antioxidant or the polyphenol content. However, I think generally speaking, many people are not aware that we ourselves cannot, with our digestive secretions, liberate those antioxidants from the cocoa. It's actually our commensal microorganisms or bacteria in the gut that liberate those polyphenols making them bioavailable for us to absorb and then utilise.  
And it's interesting that microbial fermentation is being used more and more to liberate metabolites from plant material. And what springs to mind right now is a study that I saw using resveratrol. Now, resveratrol is one of the key ingredients in red wine, attributed to its… the cardiovascular benefits and the longevity benefits that red wine has attached to it. And with resveratrol, gastrointestinally speaking, it's not particularly absorbable, and applying it to the skin, it has no absorption whatsoever. 

However, when it is fermented with microbes themselves, the compounds are liberated, broken down, and metabolised into a slurry, if you like, of phytonutrients that can cross the skin barrier. And I remember seeing the results of a half-face study done on resveratrol back when I was formulating skincare more heavily. And it was like half their faces had a facelift. It was extraordinary. 
Andrew: Wow, obviously that's got to be a pre-fermented thing though and in control.  
Amie: Yes. Correct. So it's not a matter of putting an ingredient on your face and then putting some probiotics on your face.  
Andrew: Watching it fester.  
Amie: Yes, and just giving it a good scrub and lying there. No. But it is a way in which the actives themselves are being made more bioavailable. And so that with being mindful of effective delivery systems is going to be, I think, the next step in boosting transdermal absorption 
Andrew: Okay. So the obvious one to me is skin feel. And we've spoken a little bit about, you know, which ones would be inappropriate like one that would stain the skin. But there's also greasiness and the... You know, you've mentioned the carriers and so there's that skin feel. Are they exceptionally greasy? Can they be well absorbed? And given the various factors that are going to influence absorption, how well? Like, can you put some of the nutrients on your skin and then, you know, put on a white shirt? 
Amie: Very good questions. And I think this is really the key sticking point when it comes to patient... 
Andrew: Sticking?  
Amie: That was not an intentional pun but I'll take it. So when it comes to patient compliance and ease of use and also enjoyment of use, this is an important thing to consider. And what we know so far is that the liposomal forms of nutrients, that's the most effective delivery vehicle to get things into the skin and through the skin, actually. And it really depends on whether your liposomal formula has been designed for cosmetic use or nutraceutical use. 
Andrew: And the size obviously, I'm going to... 
Amie: Yeah. Well, I guess, a side note to the quality of the liposomal formula that you're looking at. We know are that in terms of the liposome itself, the quality of the phosphatidylcholine that's used, any other things that enhance delivery and cellular retention is also key. We also need to consider things like what are the particle sizes of the active ingredients that have been applied if you're using something herbal for example.  
So all… the checklist that you would use to identify top quality liposomes for oral use, I would apply equally to anything you're going to use topically. What I will say, however, is if the liposome is a cosmeceutical that has been designed for cosmeceutical use, more thought has been put into adjusting that formula for skin feel. 

Andrew: Right. 

Amie: And if you are an aesthetician, like I am, you will have access to purchasing those. But if you are a functional medicine practitioner, chances are you're going to be looking at the range of oral liposomal products that you have at your fingertips for cosmetic use. And so, if that's the case, I will suggest that simply applying them topically is not going to be enough to achieve optimal results in a timely manner, and also have the patient look forward to using them on a regular basis. So I have some suggestions to not only improve their delivery but also improve the joyfulness of using them.  
So first of all, knowing what we know about hydrated skin being able to more readily absorb things, I would always suggest that people apply these after a warm shower or a bath. Or, if you're using it as, let's say, for example, an anti-aging facial treatment of an evening, apply it right after you've cleaned your face. And what you do want to do, or whatever part of the body you're applying this to, you want to leave the skin warm and damp.  So after cleansing has been completed, and after you've rinsed your skin, don't dry it off, leave it damp. This will allow a bit more slip so you can use less product to cover the same surface area as well as help boost the hydration of the skin. 

I would also suggest, in warm damp hands, that you emulsify the product as well. So whether that's one pump or just a few drops, you want to rub your hands together, again to really smooth that product out and allow for a better delivery. So you're not getting a whole heap of product landing in one place and not enough in another.  
In some cases, I actually recommend that it is added to a serum or a moisturiser that they would ordinarily use as well, and in that way be applied in one go. Other suggestions would be to further enhance the delivery is use something that actually does reduce the hydrolipid film and reduce the stratum corneum, and that might be something like a gentle glycolic acid peel or an enzyme wipe at home.  
And I would certainly recommend that in the case of applying say, vitamin A for acne patients, and just actually take off that stratum corneum because they typically do have retention hyperkeratosis and a thickened skin barrier and so delivery is already that much more…slightly more difficult.  

Andrew: Yeah, impeded. 
Amie: Once the product has been applied, I would also be making the recommendation to massage it in well. So don't just wipe it on like a lotion or a serum and leave it to absorb in, give yourself a facial massage or a, you know, a hand massage or really rub it into wherever you've applied the product. 

Beyond that, let's say you've done this in the evening, and you're at home, or the patient is, in the evening at home. If they can lie down with a warm damp cloth on the area, that will really help the product sink in by encouraging the circulation and the heat and the expansion of the cells.  
Andrew: Wouldn't get soaked up by the cloth? 
Amie: No, no, no. So you want the product damp, so it's not going to absorb anything but not wet, so it doesn't dilute anything. Or even a warm compress of some sort or, you know, a hot water bottle or a wheat pack, if you're using it on your leg, for example, the scar reduction. 

And then from there, you can either leave it on overnight, or for someone who… using acne is another example, whose skin might be prone to congestion, tissue off the excess before going to bed. If it has been applied to the face, I would recommend safety pinning a towel around the pillow or using an old pillow case because the product will get onto the linen, you don't want any staining and you want to be able to take it off and just wash it in the morning. Or if the product has been applied to another area, for example, vitamin C to reduce scarring and encourage wound healing, I'd be covering it with some sort of bandage overnight.  
So much of the absorption is the passive diffusion, I should say, is related to the extent with which the product is held against the skin. So by keeping it there undisturbed, you will encourage optimal absorption. 
Andrew: You know, if you're going to apply with your hands to let's say your eyes, that product is now in your hands as well. So you're going to get some absorption through the stratum corneum of your hand. 

Amie: Yep. 

Andrew: If you're talking about decreasing, you know, the wastage of the product by pinning a safety towel to your pillow, and the staining effects, and things. Well, obviously the product is in that stain, so therefore you're getting product loss through that. I'm guessing here, the critical factor here is time to get a reasonable dose, let's call that a Tmax. You know, in pharmacokinetic studies we would be look at Tmax. So has any work been done on the appropriate time to deliver the "a reasonable dose" via transdermal absorption before you can wipe it off or get rid of the product or go to sleep? 
Amie: Yes, there has, but they typically the studies have been done on single things. And because there are so many variables, particularly when it comes to skin type and how the skin has been prepared, it's difficult to give a single answer. 

From what I've read so far, 60 to 80 minutes seems to be the optimal window. 

Andrew: Gotcha. 

Amie: So if you've come home after work, and you're giving yourself a facial treatment, and you're, say, using coenzyme Q10 for its anti-aging effects or alpha lipoic acid and vitamin C for skin polishing effects. I would probably be, you know, washing my face not too long after dinner, and applying it not too dissimilarly to a face mask. But I would be leaving it on for an hour to an hour and a half. And if I was going to wash it off, it would be at that point I would wash it off before heading to bed. 
Andrew: Gotcha. Okay. But you mentioned earlier that it took, you know, 30 seconds odd to achieve this 60% to 70% absorption. Why the difference between that and the 80 odd minutes that it takes for optimal absorption? 
Amie: Well, that's actually a myth that is currently being purported you know, online, in the natural beauty community. And where it actually springs from is a 1984 study that looked at the absorption of volatile organic compounds absorbed through the skin, that are present in drinking water but the drinking water was actually applied to the skin.  
And what they found was anywhere between 29% to 91% of these volatile organic compounds crossed the skin, and were actually systemically absorbed. And on average that was 64%. And so, this one study has really been the basis for which that claim is being made. 
Andrew: Misappropriated. 
Amie: Yeah, it is. 
Andrew: That to me smacks of issues with paint, volatile organic compounds. So VOC is like a measure of toxicity, if you like, of paint? 
Amie: Sure. And contaminants in this case, in drinking water. And that's not to say the study should be disregarded, it certainly points to how permeable our skin can be. And when you consider, you know, how many tens of thousands of toxins have been introduced since World War II, only 500 of them have ever been studied for safety. We do apply and shower in a chemical cocktail with very little regard to transdermal absorption.  
Unfortunately, you cannot apply that study unilaterally and assume that anything we apply to the skin will be absorbed that readily. 
Andrew: And particularly for a therapeutic benefit. 
Amie: Absolutely. 
Andrew: Yeah. Why liposomes? What's so special about them? 
Amie: Liposomes are an incredible delivery system, not just because of their fatty nature. The liposomes themselves, in particular, the phospholipid bilayer utilise phosphatidylcholine, mimicking our own cell membrane structure. Meaning they are able to fuse, cellularly speaking, with our skin and merge as one and deliver their payload, so to speak, very, very easily. And what the evidence shows is that liposomes and the nanoparticles contained within, easily pass through the stratum corneum.  
Andrew: Intact? 
Amie: Intact. Somewhat intact, not wholly intact, but through the stratum lucidum and the granulosum, delivering their nutrients into the stratum spinosum. So there's several layers or strata of the skin. And the stratum spinosum sits right on the basal layer, which is there at the dermal-epidermal junction, and therefore just above the circulation, the subcutaneous tissues.  
So it's going to provide an effect that will directly impact the health of the skin itself. And in the event that you are attempting to deliver things systemically have the best chance, without any other third-party intervention like dermabrasion or ultrasound being applied. Optimise the delivery of those nutrients across the skin. 
Andrew: This is really interesting, Amie. So obviously there's a lot more research that needs to be done but it really opens up this new way of potential application, in certain conditions. And maybe we can get on to that at a later podcast when there's further research available. 
Amie: I would love to. I think this is a very exciting and interesting area not just with regards to improving delivery of nutraceuticals and herbal medicines, but perhaps with pharmaceutical interventions also. It's an opportunity to minimise some of the consequences of oral delivery. And I think in addition to that, the understanding of the way in which our skin allows things through into our general system will also provide us with a framework for which to view anything else we apply, including ingredients in personal care products, and the potential for the impact of those on our health as well. 
Andrew: Well, I look forward to you joining us again in the studio, and we can discuss this further, Amie. Thanks so much for joining us today. Really appreciate it. 
Amie: Thanks, Andrew. It's been a pleasure. 
Andrew: This is FX Medicine, I'm Andrew Whitfield-Cook.

Additional Resources

Amie Skilton
eBook: Clear Skin Secrets
WHO: Global prevalence of vitamin A deficiency in populations at risk 1995–2005
IVACG: International Vitamin A Consultive Group

Other podcasts with Amie include:


The information provided on FX Medicine is for educational and informational purposes only. The information provided on this site is not, nor is it intended to be, a substitute for professional advice or care. Please seek the advice of a qualified health care professional in the event something you have read here raises questions or concerns regarding your health.



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