The 500 Dalton rule for the skin penetration of chemical compounds and drugs
Jan D. Bos,M.M.H.M. Meinardi +1 more
TLDR
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.Abstract:
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.read more
Citations
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Design and Fabrication of Human Skin by Three-Dimensional Bioprinting
Vivian K. Lee,Gurtej Singh,John P. Trasatti,CS Bjornsson,Xiawei Xu,Thanh-Nga T. Tran,Seung-Schik Yoo,Guohao Dai,Pankaj Karande +8 more
TL;DR: 3D printed skin tissue was morphologically and biologically representative of in vivo human skin tissue and can be further extended for enhancing the complexity of the skin model via the incorporation of secondary and adnexal structures or the inclusion of diseased cells to serve as a model for studying the pathophysiology of skin diseases.
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Challenges and opportunities in dermal/transdermal delivery
Kalpana S. Paudel,Mikolaj Milewski,Courtney L. Swadley,Nicole K. Brogden,Priyanka Ghosh,Audra L. Stinchcomb +5 more
TL;DR: Emergence of novel techniques for skin permeation enhancement and development of methods to lessen skin irritation would widen the transdermal market for hydrophilic compounds, macromolecules and conventional drugs for new therapeutic indications.
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Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery.
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The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis when used topically under occlusion
Ulrich Mrowietz,Graeber M,Matthias Bräutigam,Thurston M,Wagenaar A,Gottfried Weidinger,Enno Christophers +6 more
TL;DR: It is concluded that the new macrolactam SDZ ASM 981 (1%) is similar to clobetasol‐17‐propionate (0.05%) in plaque‐type psoriasis when applied topically under occlusion for 2 weeks using the microplaque assay.