ABSTRACT
Perhaps no tissue is so physically maligned by processing for light/electron microscopy as is the stratum corneum (SC). To further complicate matters, no tissue of such critical importance for survival has been so intellectually maligned as well. Because routine microscopic images of normal SC depict loosely attached corneocytes (‘‘basket-weave pattern’’), until the 1960s the barrier was thought to reside not in the SC but rather in the outer stratum granulosum (SG) (Table 1). The key breakthroughs came from Albert M. Kligman’s group (Chap. 3), who found isolated SC to be not friable, but rather extremely durable (1), and from the work of Irvin Blank and Robert Scheuplein in Thomas Fitzpatrick’s department at Harvard, who further demonstrated the highly impermeable nature of the SC (2,3). Because Blank and Scheuplein found the water-transport characteristics of human SC to be similar to those of a plastic wrap, the SC soon was analogized to a sheet of plastic or ‘‘Saran’’ wrap (Table 1). According to this model, which still dominates the world view of many skin biophysicists and physical chemists, hydrophilic and lipophilic molecules traverse a uniform SC ‘‘membrane’’ via a transcellular route without regard to tissue architecture or metabolic activity (2). Accordingly, percutaneous penetration is determined by the chemical characteristics of the penetrating molecule, as well as by the diffusion path-length across the SC (thickness of the membrane), as embodied in Fick’s law (3). Although common sense alone (e.g., the hyperpermeability of the thickened SC of the palms and soles to water) immediately invalidates the ‘‘plastic wrap’’ model, the seminal work of Blank and Scheuplein nevertheless established the importance of the SC as the critical tissue determinant of the cutaneous permeability barrier. Perhaps of greater importance is that it spawned an entirely new industry devoted to transdermal drug delivery.
