A quiet analytical research laboratory at night, racks of glass vials along a dim bench.

Skin Barrier Penetration

The skin's outer layer exists to keep things out. The stratum corneum, about 10 to 20 micrometers of dead cells in a lipid matrix, blocks most molecules above about 500 Da and most highly polar ones, which limits topical peptides, NAD+ precursors and vitamin C.

How the barrier works

The stratum corneum is often described as bricks and mortar: flattened corneocytes embedded in ordered lipid lamellae of ceramides, cholesterol and fatty acids. Most molecules pass through the lipid pathway, which favors small size and moderate lipophilicity (logP about 1 to 3). Hair follicles and sweat ducts offer a secondary route. Nearly all approved transdermal drugs are under 500 Da and potent at low doses. Skin condition, anatomical site and age change barrier function.

Ways to improve delivery

Chemical enhancers such as propylene glycol, oleic acid and terpenes disrupt lipid order. Occlusion increases hydration. Carriers including liposomes, ethosomes and nanoparticles tend to accumulate in follicles and the upper stratum corneum rather than crossing intact skin. Physical methods such as microneedles, iontophoresis and lasers bypass the barrier but change the regulatory category when they breach it. Each approach is judged against skin irritation, barrier recovery time and regulatory category.

Cosmetic versus drug boundaries

A cosmetic acts on the appearance of skin. Claims of penetration into living tissue or effects on skin structure and function can make a product a drug in the US and Canada. Topical formulation claims should describe delivery to the skin surface and upper layers unless drug-level evidence exists. In the EU, a cosmetic must act on external parts of the body. Delivery data from tape stripping or Franz cells should be presented as formulation performance, not as a therapeutic effect.

Key facts

Molecules below about 500 Da penetrate skin more readily; common topical drugs fall under this limit (Bos and Meinardi 2000, Exp Dermatol)
Transdermal delivery is limited to a small set of potent, small, lipophilic drugs without enhancement (Prausnitz and Langer 2008, Nat Biotechnol)
Nanoparticles accumulate in hair follicles, which can act as a reservoir (Lademann et al. 2007, Eur J Pharm Biopharm)
An article other than food that is intended to affect the structure or any function of the body is a drug under US law (21 U.S.C. 321(g)(1)(C))

How our delivery technology applies

For topicals we design for residence, not deep penetration. Outer layers adhere to the skin surface and follicle openings and release the active gradually, keeping concentration at the stratum corneum higher for longer than a solution that dries or rinses off. Inner layers protect oxidation-prone actives such as vitamin C and NAD+ precursors in the formula. We measure delivery with tape stripping and Franz cell studies.

Request a Franz cell study for your topical active.