Lab Notes

Number 1 Priority in Layering Skincare

There are a lot of factors that you need to consider when layering products. However, one factor in particular should be the utmost priority for everyone.

reading time: 9 minutes
level: intermediate

Hi! 👋  This is the first out of four posts on the factors that affect application. Read this prioritization article to establish what your skincare priority is before moving along to understand how the barrier status gets implicated with various skincare applications. 

Tight Barrier = Goals

The goal when repairing your skin barrier is to tighten the barrier by ensuring there are enough barrier lipids (ceramides, cholesterol, and fatty acids) in your skin and that they are tightly packed. In scientific terms, the goal is to ensure that the ceramides are in their orthorhombic arrangement rather than the looser hexagonal arrangement. 

The orthorhombic arrangement is key in preventing the entry of pathogens and foreign substances, while also preventing moisture loss. However, this structure can be disadvantageous because it slows down the penetration of actives. The primary way of making actives penetrate the skin is to manipulate the Stratum Corneum (SC) through different mechanisms. For this to happen, the Skin Barrier is temporarily loosened,  allowing the penetration of actives to exert their effects. This is temporary because the skin is able to repair itself. That is, unless it’s damaged, In those cases, loosening the barrier exacerbates the damage even further. 

Hydrating Serums can cause Dryness?! Come. ON. 

Wrap your head around this. Certain ingredients in skincare products can transiently loosen the skin barrier to allow more water to reach the skin's upper layers. An example of this is Urea. As discussed in our Humectants blog, Urea changes the keratin fibers and loosens the intercellular lipids. It’s an excellent humectant clinically proven to increase hydration. However, it can also act as a penetration enhancer for other actives in your routine.

Hyaluronic acid (HA) is another example of this process. Small molecular weight HAs are currently being studied as a penetration enhancer for some drugs. The molecular weight of 5 kDa and below were shown to increase penetration of large proteins like Albumin. The exact mechanism of skin penetration is unknown, but HA also changes keratin fiber structures and intercellular lipid arrangement to increase hydration. This loosening may allow the penetration of other actives in the product. Read more about humectants here, it’s complicated but fascinating stuff. 

There are also concerns about low molecular weight HA (<50/250 kDa) being pro-inflammatory. This makes sense as HA fragments serve as indicators that the skin has been breached. Think of HA under the skin as soft, fluffy down feather pillows. They make your skin super plump and smooth, especially when you're young. When you damage the skin, you inadvertently damage the "pillows" underneath and this scatters the  down feathers (HA fragments) everywhere. When your cells see those down feathers, they would know for sure that your skin got damaged and they would trigger an alarm for a breach. This signals your inflammatory and repair cells to arrive at the site of damage. Although there are a few studies done on LMW HA, more studies need to be done to understand this concept fully.


Acids Enhance Penetration

Another way of enhancing skin penetration is through Acids. AHAs and BHAs are desquamating agents that can degrade desmosomes and tight junctions depending on the concentration and the type. The theory is that they can sequester or chelate Calcium ions in the skin, which leads to the degradation of the desmosome. In English, (lol) this means that AHA loosens the skin by degrading the structure that holds cells together. They promote the penetration of actives by creating pockets to facilitate easy penetration.

For this reason, AHAs and BHAs are good potentiating products to use with some actives like Retinol. The downside to increased penetration is that it also potentiates irritation. No matter how mild AHAs and BHAs are, using them daily, even in low concentrations (1% AHA/ 0.5% BHA), leads to some cellular toxicity, which can be aggravated by Retinol. 

Focused on Pigmentation and Texture? 

If you are focused on Pigmentation and Texture, using AHAs and BHAs as potentiators would be a good idea to supplement the active you use. Start slowly at 8% AHA 2X a week and gradually increase it to every other day. However, if your priority is barrier repair, you should consider switching to PHAs as they promote tight junctions that are an essential part of your Barrier. It was shown that PHA concentrations of 2-6% could upregulate tight junctions in the skin more effectively than AHAs. 


There are a lot of penetration enhancers that are being used in skincare and we also use them because some actives are really hard to get in the skin. Here is a list of common penetration enhancers used in skincare:

Do these Penetration Enhancers Need to be Totally Avoided? 

This is where prioritization comes in. It’s crucial to determine your main priority, as it determines how to proceed in your layering. If you have a healthy skin barrier, some of these penetration enhancers may enhance your skin as they deliver actives to the deeper layers of your skin. However, if you are just starting to repair your moisture barrier, it would be best to focus on tightening your barrier and wait to use high concentrations of barrier looseners, until your barrier can handle it. 

Notice that we said high concentrations; some of these penetration enhancers can be exceptions to the rules depending on their environment and concentration. Let's take Linoleic acid as an example. By itself, Linoleic acid is a penetration enhancer because it rearranges the barrier lipids. However, if applied together with Barrier Lipids like Ceramides, Cholesterol and Non-essential Fatty acids in a proper ratio, it can improve barrier function. 

tl;dr: when repairing the barrier, postpone barrier looseners. When the barrier is repaired, proceed cautiously with everything you apply.