Transdermal delivery of inorganic complexes as metal drugs or nutritional supplements.

The gastro-intestinal tract presents a significant barrier to the efficient absorption of both orally administered metal drugs and dietary essential trace minerals. Absorption can be compromised by competition between alimentary metal ions, by an excess of dietary ligands (e.g. polyphosphates), or by disease (e.g. chronic inflammation). Alternative delivery by injection can be expensive, painful, often promotes systemic toxicity and usually leads to rapid elimination through excretion (bile, urine), as a consequence of bolus dosing. By contrast, our new observations indicate that presenting trace metals or metal drugs in lipophilic forms which can penetrate the dermis, permits their slow release from the skin with more efficient (relative to incipient toxicity) systemic delivery. Examples are given from our own research of dermal application of copper(II), zinc(II), titanium(IV), platinum(II) and gold(I) complexes to treat chronic inflammatory disease. Some of these compounds are also anti-cancer agents. Physical and biological constraints to transdermal (percutaneous) drug delivery are discussed together with some chemical principles governing selection of complexes as metal drugs or dietary supplements.