Skin Deep

Delivery systems and skincare absorption

There are a lot of factors that go into formulating skincare, but surprisingly, penetration strategies are often overlooked. These strategies are critical to the efficacy of products, including a review of the pathways skincare ingredients use to get in. It is also important to identify backbar strategies and the pros and cons of popular methods to improve absorption during facials. The skin is a remarkable organ that works 24/7 to keep most things out, so the challenge is daunting.

Most skincare formulators and skincare professionals give little consideration to the challenges of penetrating skincare past the surface lipids. Approximately 2-5% of the ingredients that are applied to the skin actually makes it past the stratum corneum. That is a lot of waste. Unless the ingredients are designed to create surface plumping, such as hyaluronic acid, they do very little to help the skin’s appearance and virtually nothing to accelerate healing.

What is the biggest problem?

For those who know the ‘500 Dalton Rule’, the biggest issue in skincare absorption is the molecular size of ingredients. Ingredient size can be measured in Daltons, and anything more than 500 Daltons appears to have a lot more trouble penetrating through the epidermal layers. All of the known substances that create contact allergies are smaller than 500 Daltons implying that something cannot be an allergen unless it can penetrate through the barrier.

While molecular size is significant, larger molecules still have a chance to penetrate if they find the right pathway.

[ihc-hide-content ihc_mb_type=”show” ihc_mb_who=”2,4,5,6,7″ ihc_mb_template=”3″ ]

Here is a list of commonly used ingredients in skincare and their sizes:

• Retinol = 286 Daltons

• Ascorbic Acid = 176 Daltons

• Tetrahexyldecyl Ascorbate = 1130 Daltons

• GHK-Cu = 404 Daltons

• Palmitoyl oligopeptide = 579 Daltons

• Hyaluronic Acid = 800-80,000 Daltons

You can see why some of these might have more trouble getting into the skin. While molecular size is significant, larger molecules still have a chance to penetrate if they find the right pathway. Evidence suggests that if an ingredient can get past the lipid barrier, it may continue to make its way to the basement membrane and even into the dermis.

Getting Past the Barrier

There has been surprisingly little research done on measuring the concentration of various actives at the dermal level after application. However, it can be assumed that the skin, being highly intelligent, preferentially incorporates substances that it recognizes as beneficial. That is not to say that if a toxin gets past the barrier, the skin will kick it back out, but more of the inactive, harmful and/or ineffective ingredients likely end up in epidermal purgatory than the good stuff.

This speaks to another issue in ingredient absorption, bioavailability. Many ingredients are modified using lipophilic (fat-loving) attachments that can help them slip by the barrier but may also limit what happens after that. We learned a decade ago that C-esters (ascorbyl palmitate) have such a strong bond that the skin could not separate them. Therefore, the ingredients were not active.

This same issue appears to be happening with THD-ascorbate (ascorbyl isopalmitate). These two can be differentiated from retinyl palmitate for which the skin has a mechanism to split it off if needed. While retinyl palmitate is more lipophilic than retinol, it is also over 500 Daltons. This means there is no advantage in penetration. Some makers of liposomal ingredients use materials that blend well (are both water and lipid-soluble) and pass through the barrier fine but never release into the skin.

That being said, liposomes can be an effective way to enhance penetration if appropriately designed. While there is some debate as to the preferred type of liposome, pharmaceutical companies have done the clinical trials to show that liposomes are the best chance for transdermal penetration. Research shows as much as a 600% increase in overall absorption, which equates to improving penetration from 5% to 30%. That goes a long way in improving the odds that a product can make real changes to the skin.

The best liposome is made from phosphatidylcholine because that is what the cell walls are made of, and it offers UVB protection and improved moisture retention as a bonus. When made using a pharmaceutical-grade fluidizer, the liposomes hold up well. While there is no question that lipidbased products penetrate more effectively, 90% of the critical actives people need/use in skincare are water-soluble and need a penetration strategy like liposomes.

When an ingredient is larger than 500 Daltons, it has to pass through the follicle in order to have a chance at being active in the skin. This applies to many growth factors, most peptides that have four or more amino acids, and a host of larger ingredients. The follicle reaches into the dermis, but there are still some structural limitations to what gets through. Approximately 80% of skincare passes through the stratum corneum by migrating between cells (intradermal) or by entering and exiting through cell walls (transdermal), whereas 20% penetrates through the follicles.


Beyond the lipid-loving properties and molecular size, another factor in improving penetration is the concentration. In other words, the more dense the serum, the better the penetration rate. This has more to do with osmosis and the balancing of nutrients between cells. Don’t confuse this with the studies on Vitamin C that showed a lower pH is helpful. Most research supports that lowering pH is not a factor in penetration unless it involves damaging the barrier in the process. This is the net effect of the most quoted Vitamin C study by Dr. Pinnell. They melted the skin with a low pH serum and an occlusive bandage, which will improve penetration as the skin barrier deteriorates over those 24 hours. Without an occlusive bandage, lower pH is not helpful.

In the Treatment Room

This leads to a common tactic by many skincare professionals that involves damaging the barrier to improve penetration. It is still the most common approach taken by most skincare companies and estheticians. Alcohol or acid-based toner is often in the protocol to exfoliate and remove the lipid barrier in preparation for the serum application. In treatment rooms, you will find acetone, scrubs, and acid peels as the go-to methods for penetration enhancement.

Doing this every 4-6 weeks is tolerable, but the daily attack on the skin’s protective barrier is a practice that increases sensitivity, sun damage, skin cancer, and skin dehydration. It takes three days for the skin to recover from wiping it with acetone, it takes a week for the barrier to recover from moderate microdermabrasion and two weeks for a mild-moderate acid peel. Yes, there are added benefits to increasing the absorption of facial products in most cases, but the inflammation, DNA damage, and compromised skin are not worth it.

Microneedling is another example of a strategy to increase penetration. Again this adds to the wounding of the skin to try and get more actives in. Some people think the wounding process is rejuvenating. However, I do not subscribe to that philosophy. There is a net gain in penetration but not as much as you might think because a wounded epidermis heals from the bottom up, and this can push some ingredients back out.

Instead, it is beneficial to create temporary, shallow microchannels in the stratum corneum (using a Revitapen) that allow the nutrients to get in without any long term effects on the health of the skin. This allows the skin to focus all of its attention on what is being absorbed without having to distract itself by fixing the epidermis.

A Closer Look at Skincare

Absorption strategies should be one of the most important aspects to look at when evaluating a skincare line. Improved delivery of bioavailable ingredients means more healing, more protection, and more collagen activation. Avoiding strategies that harm the barrier means healthier, less sensitized skin. Please reconsider any routine that exfoliates or strips lipids every day.

Analyze your skincare products to see if they employ methods like high concentration serums, delivery systems, bioavailable ingredients, Dalton size considerations, etc. It is very, very hard to create permanent changes in the skin, so you need to address every bottleneck to achieve this, penetration of actives being one of the most important.