Department of Dermatology, Academic Medical Center, University of
Amsterdam, The Netherlands.
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.
Publication Types:
Review
Review, tutorial
PMID: 10839713 [PubMed - indexed
