The skin is like a fly screen. It allows toxins out and oxygen in, but screens out larger substances which could otherwise be detrimental to the body. To enter the epidermis, a substance must have a molecular weight (size) less than 3,000. To enter the cell, it must be below 800. Substances below 75 can enter the bloodstream. 99% of ingredients used in cosmetic products have a high molecular weight which prevents them from entering the skin at all. A few well refined formulations have molecular weights as low as 2,000 which means they can enter the outer layers of the skin, but are still too large to work at a cellular level. The medical industry uses a special process by which almost any substance can be reduced in molecular weight. This process is used to create formulations for use typically in hormone replacement therapy and nicotine patches. There is only one company that we are aware of which owns the patented rights this the high-tech molecular reduction process for use in skin care products.
With age or poor nutrition, collagen levels in the skin can be depleted. This causes the skin to become thinner and sag. However in the form it is used in cosmetics, collagen has a large molecular size (molecular weight = 300,000) which is too large to penetrate the skin. Consequently it sits on the surface of the skin, clogs the pores and inhibits its ability to expel toxins and wastes. Collagen sources used commonly in cosmetics are from sources which are incompatible with human skin. Collagen implant injections administered by plastic surgeons to reduce wrinkles are treated by the body as an alien substance and systematically removed. Additional collagen injections are needed every six to twelve months to maintain the appearance desired.
Human skin has unique properties of which functioning as a physicochemical barrier is one of the most apparent. The human integument is able to resist the penetration of many molecules. However, especially smaller molecules can surpass transcutaneously. They are able to go by the corneal layer, which is thought to form the main deterrent. We argue that the molecular weight (MW) of a compound must be under 500 Dalton to allow skin absorption. Larger molecules cannot pass the corneal layer. Arguments for this "500 Dalton rule" are;
1) virtually all common contact allergens are under 500 Dalton, larger molecules are not known as contact sensitizers. They cannot penetrate and thus cannot act as allergens in man;
2) the most commonly used pharmacological agents applied in topical dermatotherapy are all under 500 Dalton;
3) all known topical drugs used in transdermal drug-delivery systems are under 500 Dalton. In addition, clinical experience with topical agents such as cyclosporine, tacrolimus and ascomycins gives further arguments for the reality of the 500 Dalton rule. For pharmaceutical development purposes, it seems logical to restrict the development of new innovative compounds to a MW of under 500 Dalton, when topical dermatological therapy or percutaneous systemic therapy or vaccination is the objective.