Research Summary
Human skin has unique properties, one of the most apparent being its function as a physicochemical barrier. The human integument is able to resist the penetration of many molecules. However, smaller molecules, in particular, can surpass transcutaneously. They are able to pass through the corneal layer, which is thought to be the main deterrent. We argue that the molecular weight (MW) of a compound must be under 500 Daltons 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 Daltons, as larger molecules are not known as contact sensitizers since they cannot penetrate and, therefore, cannot act as allergens in humans; 2) the most commonly used pharmacological agents applied in topical dermatotherapy are all under 500 Daltons; 3) all known topical drugs used in transdermal drug-delivery systems are under 500 Daltons.
Further evidence supporting the 500 Dalton rule comes from the use of drugs such as cyclosporine, tacrolimus, and ascomycins. For topical dermatological therapy, percutaneous systemic therapy, or vaccination purposes, it seems logical to restrict the development of new innovative compounds to a molecular weight of under 500 Daltons.
Keywords: drug design, skin, topical drugs, transdermal.
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