How ingredients are absorbed by our skin (and why you should care)
Skin, a semi-permeable barrier
I don’t know about you, but it took me a LONG time to learn the lesson that my skin is more permeable than I think. This realization dramatically impacts which ingredients I choose to put on my skin.
Of course, skin isn’t equally permeable to all ingredients, and today we’re going to take a look at some of the main factors impacting skin absorption. Yeah, there’s some science talk in here, but I’ll guide you through it.
First off, some definitions.
While there is a technical difference between penetration, permeation, and absorption, we do not make that distinction in this article and use these three terms interchangeably throughout this blog post to mean the same thing - whether the ingredient is pulled into the living layers of skin (i.e whether it penetrates the dead skin cell layers of the stratum corneum).
Let’s start out with a recap of skin anatomy.
The skin is composed of the epidermis, dermis, and a subcutaneous fat layer. Let’s not forget about hair follicles, which are rooted in the dermis but extend all the way to the surface.
Figure 1. Overview of skin layers1.
Now, let’s take a closer look at that outermost layer, the epidermis. The epidermis itself is composed of multiple layers as shown in Figure 2 below. The stratum corneum, the outermost layer of the epidermis, is actually dead skin of varying thickness depending on what part of the body we’re talking about.
The stratum corneum of our face is roughly 15 to 20 cell layers thick. These are dead cells, so while there’s still an intact cell membrane, there’s no active transport across the cell membrane as there is in living cells – the active transport proteins get removed during a process called keratinization, and if you want to read more about this process, visit our previous blog post here.
Figure 2. Zoom view of the epidermal layer of skin showing the dead skin layers (stratum corneum) and viable skin layers of the epidermis2.
Before we move on, we need to take a look at the structure of the cell membrane, specifically cells of the stratum corneum.
Figure 3 shows a picture of the cell membrane, and the important thing to notice is the lipid bilayer. Let’s talk about that left inset in this figure. The blue circles in that inset represent a hydrophilic (water loving) head and the dark squiggles represent a hydrophobic (water fearing) tail. The job of this bilayer is to keep hydrophilic molecules from entering or leaving the cell because water loving ingredients cannot penetrate into the hydrophobic interior of the bilayer. In case you skip this part (or space out), we’ll define these terms again later.
Figure 3. Composition of the cell membranes in the stratum corneum. Note, these cells lack any active means of transport making their cell membrane structure different from living cells3.
Now that we’ve revisited our anatomy, let’s talk about how ingredients can get down to the living skin layers.
There are three routes of entry through the stratum corneum:
- Intracellular pathway – this is where an ingredient diffuses directly through the cells of the stratum corneum. That means the ingredient has to migrate through the lipid bilayers of every cell membrane (remember, the stratum corneum is 15 to 20 cell layers) on its way from the skin’s surface down to viable skin layers.
- Intercellular pathway – an ingredient can bypass the cells of the stratum corneum entirely by traveling between cells.
- Transappendageal pathway – ingredients can also travel down sweat glands or hair follicles. This pathway only accounts for a small percentage of absorption.
Here’s a visual.
Figure 4. Possible pathways for ingredients to travel from the skin’s surface into living skin layers4.
Now that we’re done with the recap, let’s get right to it!
Let’s start with the easy stuff first.
Thickness of the stratum corneum
The thickness of the stratum corneum varies depending on where on the body we’re talking about. We’re concerned about our face in this post, so we’re talking 15 to 20 cell layers thick.
Concentration of the ingredient in the product
The concentration of a product’s ingredients impact how quickly those ingredients penetrate the skin. The higher the concentration, the faster the migration from the surface of the skin into viable skin layers.
Pretty simple, right?
Okay, done with the easy stuff, let’s jump on into the other factors.
Molecular Weight of the Ingredient plays a role in skin permeation
Before you check out by seeing the term ‘molecular weight’, let me bring you back with something interesting like ‘hyaluronic acid’.
Now that I’ve got your attention again, we need to establish a couple points before linking those two terms. Studies show that ingredients up to a molecular weight of around 500 Daltons are capable of penetrating the skin within a reasonable time period.
What’s a Dalton? We’re just talking about the size of the molecule, and molecules are SO small it’s hard to talk about them in terms of ounces and pounds, so scientists came up with the fancy word Dalton. Dalton is an expression of molecular weight and is synonymous with atomic mass unit and grams per mol.
For some context, let’s look at a few common skincare ingredients:
- Water – 18 Daltons
- Vitamin C – 176 Daltons
- Magnesium Ascorbyl Phosphate (stabilized Vitamin C) – 278 Daltons
- Hyaluronic Acid (Ultra Low Molecular Weight) – less than 6,000 Daltons
- Hyaluronic Acid (High Molecular Weight) – between 8,000 and 12,000 Daltons
- Peptide – Diaminopropionoyl Tripeptide-33 (aka Preventhelia) – 374 Daltons
What is ‘a reasonable time period’? Well, formulation development scientists for topical drugs (think Retin-A and Differin) evaluate something known as flux when looking at skin permeability of potential drug products. Flux simply means how fast an ingredient travels through layers of skin.
Let’s pause for an illustration. Imagine each of the ingredients in your skincare product is a person and the stratum corneum is a doorway. Let’s pretend water is the size of a 4-year old and stabilized Vitamin C is the size of an NFL player. Three or four 4-year olds might rush through the doorway at once, but only one linebacker is coming through that door at a time.
Before moving on, let’s mention the elephant in the room. High molecular weight hyaluronic acid isn’t coming through that doorway! Besides, that’s not the point of that ingredient anyways – hyaluronic acid is intended to form a protective barrier on the skin’s surface to prevent trans epidermal water loss, but I digress, so let’s get back to the topic at hand.
We’re not done talking about factors influencing skin penetration, so let’s keep going.
Solubility of an ingredient
Alright, so we all know oil and water don’t mix (think of that oil and vinegar dressing you used at lunch – the balsamic vinegar, which is water-based, sinks to the bottom while the olive oil floats on top).
Coenzyme Q-10 and Vitamin E are the best examples of commonly encountered ingredients in skincare products that are NOT soluble in water. Compounds like these are called hydrophobic – literally translated ‘afraid of water’.
Meet Abe, he’s also afraid of water 😊.
If you remember back to where we talked about pathways of absorption, the oil soluble (hydrophobic) ingredients can penetrate through the stratum corneum along the intracellular route by traveling through the cells of the stratum corneum. And, water soluble (hydrophilic) ingredients penetrate the stratum corneum either through the intercellular route (moving between the cells of the stratum corneum) or along the transappendage route.
How does solubility fit into the example?
Imagine there are other folks milling around the doorway (grandparents and football fans). These folks are happy chatting outside the doorway but provide an added impedance for the children and football players trying to make it inside. The children, being water loving, dodge and weave between outstretched arms to traverse through the doorway ( intracellular example) or are swept up by a hurried parent and whisked inside (transappendage example). The NFL players take the time to visit with their fans before making it through the doorway, making the NFL players like the hydrophobic molecules that have to move through the cells (the tailgaters) on their way inside.
Putting it all together
A variety of factors impact how well an ingredient penetrates the skin. Here’s the summary of the major factors:
- The area of the body to which the ingredient is applied.
- The concentration of the ingredient in the product
- The size of the ingredient
- The water loving or water fearing nature of the molecule
Some Ingredients Enhance Skin Penetration
Now, it’s possible to enhance skin permeability of ingredients by using penetration enhancers. Penetration enchancing ingredients disrupt the barrier function of the stratum corneum making it easier for themselves and other ingredients to move through the stratum corneum.
What ingredients act as penetration enhancers? Studies since the 1980s show that essential oils can aid skin penetration5,6 of other ingredients. Essential oils work so well at enhancing skin permeability that they have been used as penetration enhancers for delivery of topically applied drug ingredients6.
Now, this isn’t the only reason essential oils are used in products. Essential oils impart their own skincare characteristics – think bisabolol in chamomile essential oil to help soothe skin – into products as well and may be used for that purpose alone. And, there are many other ingredients that can enhance skin penetration like cosmoperine (a molecule derived from peppercorns).
How do penetration enhancers fit into our example? Well, imagine Marshmello walks up.
Naturally, the grandparents and tailgaters get distracted and move away from the doorway giving the children and NFL players the window they need to rush the door. The same thing happens when penetration enhancers, be that essential oils or other ingredients, are added to a formulation to aid skin penetration.
Now that you’ve had a crash course in skin absorption, how do you feel about your current skincare products? Are you thinking about reevaluating the need for multiple leave on products?
I know I did! It's also one of the reasons I started making my own skincare products... to minimize my exposure to unnecessary and questionable ingredients.
And, that's what Return to Eden is all about, packing as many good ingredients as possible into a single product while limiting the use of any unnecessary ingredient. It's as clean as we can get it without aseptic manufacturing (which none of us can afford anyways). To shop these products, click here
If this blog post raises more questions than answers, don’t worry, we’re here to help! Just reach out to us for any questions you have big or small about skincare ingredients. And, rest assured, we’ve taken skin absorption into account during product development.
5A.C.Williams and B.W.Barry Essential oils as novel human skin penetration enhancers panel. https://doi.org/10.1016/0378-5173(89)90310-4
6Anna Herman and Andrzej P. Herman. Essential oils and their constituents as skin penetration enhancer for transdermal drug delivery: a review. First published: 31 December 2014. https://doi.org/10.1111/jphp.12334