Targeting local tissues by transdermal application: Understanding drug physicochemical properties that best exploit protein binding and blood flow effects

The targeting of topically applied drug molecules into tissues below a site of application requires an understanding of the complex interrelationships between the drug, its formulation, the barrier properties of the skin, and the physiological processes occurring below the skin that are responsible for drug clearance from the site, tissue, and/or systemic distribution and eventual elimination. There is still a certain amount of controversy over t he ability of topically applied drugs to penetrate into deeper tissues by d iffusion or whether this occurs by redistribution in the systemic circulati on. The major focus of our work in this area has been in determining how ch anges in drug structure and physicochemical properties, such as protein bin ding and lipophilicity, affect drug clearance into the local dermal microci rculation and lymphatics, as well as subsequent distribution into deeper ti ssues below an application site. The present study outlines our recent thin king on the drug molecule optimal physical attributes, in terms of plasma a nd tissue partitioning behaviour, that offer the greatest potential for dee p tissue targeting. Drug Dev. Res. 46:309-315, 1999. (C) 1999 Wiley-Liss, I nc.