Characterization of molecular transport across human stratum corneum in vivo

Abstract

A percutaneously delivered therapeutic agent, whether directed at the systemic circulation or the local tissues, must traverse the stratum corneum (SC), which effectively restricts molecular transport between the external environment and the interior of the human body. The composition of the SC, and the highly tortuous nature of the extracellular pathway (1), makes this relatively thin biomembrane perhaps the body’s most efficient barrier. This has been a great boon to the transdermal formulation scientist, who can effortlessly evaluate transcutaneous drug transport by relatively uncomplicated in vitro diffusion experiments using excised or “simulated” skin. These experiments have been, and remain, instrumental to the preliminary screening of transdermal candidates, formulation excipients, and in mechanistic assessments, but, as with all methodology, present a number of obvious limitations, which collectively generate a cogent argument for human in vivo evaluations in many situations. First, the SC unfortunately lacks the consistent performance desirable of most synthetic rate-determining membranes in that its barrier properties vary both