Size Does Still Matter: Molecular Weight, Penetration & the Physical and Chemical Rules of Skin

Are your skincare actives actually penetrating your skin, or do they remain on the surface like water beading on a leaf?

This phenomenon, known as the lotus effect was first studied in lotus leaves and occurs because highly hydrophobic (water hating) surfaces repel water rather than absorb it. Human skin behaves in much the same way. The skin barrier is inherently lipophilic (fat loving) and resistant to penetration, and skincare ingredients with a molecular weight greater than ~500 Daltons remain surface-bound, regardless of how they are marketed. The skin barrier is designed this way, and that design is precisely what makes it highly effective in protecting our internal environment from a constantly changing external one.

Understanding how (and whether) ingredients penetrate the skin is one of the most misunderstood topics in skincare. Bigger claims do not mean deeper delivery, and “active” does not automatically mean bio-available.

The Skin Barrier Is Not a Flaw to be Overcome. It is a Critical Feature keeping us Safe

Your skin’s outermost layer, the stratum corneum, exists for one primary reason, to protect you.

It is a highly specialised, living barrier with interrelated functions designed to:

• Keep allergens, microbes, pollution, and toxins out

• Retain hydration within the skin

• Regulate inflammatory and immune responses

• Maintain systemic homeostasis (temperature and fluid balance)

When skincare ignores the physical and chemical reality of how the skin barrier functions, it does not become more effective, it becomes compromising, disruptive, and damaging.

Penetration vs Absorption (They Are Not the Same)

These terms are often used interchangeably, but they describe very different processes.

• Penetration refers to a substance entering the layers of the skin barrier, whether it accumulates in the stratum corneum, viable epidermis, or dermis.

• Absorption occurs after penetration, when a substance enters the vascular system and circulates throughout the body.

If a compound does not penetrate the stratum corneum, absorption cannot occur.

The 500 Dalton Rule

Human skin obeys the laws of physics and chemistry. Not marketing claims.

The 500 Dalton Rule states that:

Any molecule with a molecular weight greater than ~500 Daltons cannot penetrate healthy, intact human skin without manipulation.

This rule is supported by decades of dermatological and pharmacological research and explains why:

• Most contact allergens are under 500 Daltons

• Topical drugs used in transdermal delivery systems are under 500 Daltons

• Large molecules do not function as allergens because they cannot penetrate

If a molecule is too large, it stays on the surface.

Why Water, Vitamin C & Hyaluronic Acid Don’t Penetrate

The skin barrier is lipophilic (fat-loving), not hydrophilic (water-loving).

This means:

• Water does not penetrate the skin

• Vitamin C (ascorbic acid) is water-soluble and chemically unstable

• Hyaluronic acid — even “low molecular weight” versions which range from approximately 10,000 to 1,000,000 Daltons, making it 20–2,000 times too large to penetrate intact skin

These ingredients appear to “work,” typically due to a temporary surface hydration or artificial plumping, barrier disruption, not true penetration into the layers of the skin and bio-activity.

If You Can Smell It, It’s Small Enough to Penetrate and Irritate causing Inflammation and Oxidative Stress

Volatile aromatic compounds must be small to be detected by our olfactory system.

In practical terms:

• Most fragrance molecules are under 300 Daltons

• This makes them highly penetrable

• Which is why they are classified as contact allergens

Essential oils and fragrance compounds readily penetrate the skin barrier and can induce inflammation, increase oxidative stress, and reduce cellular antioxidant capacity, even when the skin appears unaffected on the surface.

How Ingredients Cross the Skin Barrier

There are only three pathways through which substances can cross the skin barrier:

1. Intercellular lipid matrix
   (the primary lipophilic pathway composed of ceramides, cholesterol, and free fatty acids)

2. Corneocytes
   (densely packed, keratin-rich cells, the most resistant route)

3. Appendageal pathways
   (hair follicles, sweat glands, and sebaceous glands, limited surface area)

This is why molecular size and solubility matter. If an ingredient does not follow the physical and chemical rules of the skin barrier, it will remain on the surface.

Penetration Enhancers: The Hidden Cost of “Results”

Many skincare products rely on chemical penetration enhancers to force ingredients into the skin.

Common examples include:

• Water (temporarily swells corneocytes, increasing permeability while disrupting intercellular lipid organisation)

• Alcohol and ethanol

• Glycerol

• Propylene glycol (PEG's)

• Urea

• Surfactants

• Terpenes (aromatic compounds)

• Oleic acid (dominant in olive oil and many plant oils and butters)

These substances work by disrupting the stratum corneum and increasing permeability.

Disruption, whether chemical or physical, damages the skin barrier and increases vulnerability to inflammation, allergens, microbes, impaired skin integrity, and systemic exposure.
Microneedling and exfoliation are physical examples of the same principle, they damage the skin barrier.

What True Skincare Should Do

The goal of skincare is not to override your skin’s biological intelligence.

It is to support and reinforce the barrier and to boost the skin’s natural antioxidant defences, not bypass them or provoke inflammation and oxidative stress.

Some substances are meant to remain on the surface to protect it:

• Mineral sunscreen

• Insect repellents

• Antiseptics

Skincare ingredients must penetrate to influence cell signalling, skin function, cell response and create foundational change only if their size, structure, and chemistry align with skin physiology.

Why New “Actives” Still Don’t Comply With the Fundamental Laws of Skin Physics and Chemistry,

Despite rapid innovation in skincare marketing, the fundamental physics and chemistry of human skin have not changed. Emerging “actives” such as exosomes, growth factors, salmon sperm DNA, NAD⁺, peptides, and so-called stem cell extracts do not bypass the biological constraints of the stratum corneum. Many of these compounds are biologically large (often thousands to millions of Daltons), highly hydrophilic (water loving), electrically charged, or structurally unstable in topical formulations. As a result, they cannot penetrate healthy, intact skin without physical or chemical barrier disruption.

When effects are reported, they are typically due to surface-level hydration, occlusion, inflammation-mediated signalling, or the use of penetration enhancers that compromise barrier integrity. No topical ingredient, regardless of how novel or biologically complex,  can violate the established relationship between molecular size, solubility, and skin permeability. Marketing trends evolve. The laws governing skin penetration do not. If exosomes were able to penetrate the skin barrier, microneedling would not be required.

Skin Longevity Requires Barrier Integrity, Not Forced Penetration

Skin longevity is not achieved by repeatedly forcing ingredients through the barrier, but by preserving and supporting the structure and function of the barrier itself. Chronic barrier disruption accelerates inflammation, increases oxidative stress, impairs lipid synthesis, and compromises the skin’s ability to regenerate and defend itself over time. Healthy skin ages more slowly because it is protected, not breached.

Why Vitis V Face TonIQ Is Different

Vitis V Face TonIQ is blended not formulated and does not contain penetration enhancers, surfactants, preservatives, fragrance, or inflammatory compounds.

Its bio-activity comes from naturally occurring, skin-compatible molecules that respect the rules of the skin barrier.

Key Lipophilic Compounds (Daltons)

• Linoleic acid — 280.5

• γ-tocotrienol — 410.6

• α-tocotrienol — 424.7

• β-sitosterol — 414.7

• Stigmasterol — 412.7

• Campesterol — 400.7

• β-carotene — 536.9
  (converted in-skin to retinyl esters ~302.5)

Hydrophilic Compounds

• Proanthocyanidins — ~592.5
  (composed of catechin/epicatechin units ~290.3)

While intact proanthocyanidins remain surface-bound, where they protect against UV damage and exert anti-inflammatory effects. Their smaller constituent units and antioxidant interactions support the skin’s defence systems and bind to skin-damaging enzymes involved in collagen degradation, elastin breakdown, and hyperpigmentation. These compounds neutralise damaging oxidative reactions without disrupting the skin barrier.

Small Does Not Always Mean Safe

Not all penetrable molecules are beneficial.

Fragrance and essential oils penetrate easily and frequently provoke inflammation, oxidative stress, and reduced cellular antioxidant capacity. This is why Vitis V Face TonIQ is unscented and fragrance-free by design, not omission.

True Skincare Works With Your Biology

Your skin barrier is not something to outsmart.

It is something to respect.

Be cautious of skincare that promises "actives" without explaining how penetration is achieved or at what cost to your long term skin health. A quick search of an ingredient’s molecular weight can be revealing. True skin health comes from ingredients that work with your biology, not against it.

Vitis V Face TonIQ delivers bio-available, skin-essential compounds that nourish, protect, and strengthen the barrier without forcing entry.

Because when it comes to skin, the physical & chemical rules exist for a reason, to keep us safe. Why would you want to compromise, disrupt or damage that? In fact don't mess with your skin barrier. Your older self will thank you.

References 

The 500 Dalton rule for the skin penetration of chemical compounds and drugs

https://onlinelibrary.wiley.com/doi/full/10.1111/srt.12968

https://biomeddermatol.biomedcentral.com/articles/10.1186/s41702-020-0058-7

Oligomeric Proanthocyanidins: An Updated Review of Their Natural Sources, Synthesis, and Potentials