An ingredient list names an active, but it says nothing about how much of that active actually reaches the skin layer it needs to. The gap between the two is the subject of percutaneous bioavailability research, and it explains why the same compound in two dosage forms produces different measured outcomes.
This article summarises the three factors most consistently reported in the peer-reviewed literature: the structure of the stratum corneum barrier, the molecular weight of the active, and the role of the carrier vehicle.
The Stratum Corneum and the 500 Dalton Rule
The stratum corneum is roughly 10–20 micrometres thick and consists of corneocytes embedded in an intercellular lipid matrix. This structure evolved to retain water and exclude external matter, which means by default it also excludes cosmetic actives.
Bos and Meinardi (2000) reviewed skin penetration data and proposed an empirical threshold: nearly every compound observed to cross intact skin has a molecular weight below 500 Daltons. This is not a physical law but a rule of thumb, and it remains a common reference point when assessing a formulation.
The direct consequence: a small-molecule active may act in deeper layers, while a large molecule largely remains at the surface and acts through a different mechanism.
Why a Serum Differs From a Cream
A serum is typically an aqueous or water–glycol system with a low oil-phase fraction. Less oil phase means less material holding the active within the formulation, so water-soluble actives tend to partition onto the skin surface faster than they would from a heavy emulsion.
In exchange, a thin texture also means fewer occlusive components. Serums are therefore usually described in the literature as an active-delivery step, with moisture retention left to the product applied afterwards — two distinct roles, not interchangeable ones.
Aloe Polysaccharides: Large Molecules, a Different Mechanism
Hamman (2008) describes aloe leaf gel as containing long-chain polysaccharides as its principal actives, with acemannan having a molecular weight on the order of tens to hundreds of thousands of Daltons — far above the 500 Dalton threshold above.
This does not mean the compound class is inert on skin. It means the reported mechanism is superficial: forming a water-retaining film and attracting moisture, rather than penetrating into the dermis. Distinguishing these two mechanisms is exactly where product copy tends to overstate.
Limits of the Current Evidence
Most percutaneous data come from excised skin in Franz diffusion cells — that is, laboratory conditions rather than living skin with circulation and sebaceous activity. Results should therefore be read as a ranking between formulations, not as absolute figures for any individual user.
The above is scientific information and is not a substitute for medical diagnosis, advice or treatment. Please consult a dermatologist for any skin condition requiring follow-up.
