Molecular transport of electroactive molecules through human and hairless mouse skin

This dissertation describes molecular transport across biological membranes (human skin and hairless mouse skin) and artificial membranes (mica/Nafion membranes). Chapter 1 provides an overview of the structure of human skin. Chapter 2 provides an overview of basic principles underlying this dissertation, outlining the basic equations and descriptions of molecular transport.; Chapter 3 describes the characterization of scanning electrochemical microscopy (SECM) tips used to study molecular transport in skin. Two types of tips are investigated: carbon fiber and etched platinum tips. The carbon fiber tips are cylindrically shaped, while the platinum tips have a more tapered, hemispherical geometry. The tapered geometry of the platinum electrodes is less obstructive in molecular transport compared to the cylindrical electrodes.; An investigation is reported in Chapter 4 of the origin of electroosmotic flow in human skin. SECM is used to measure electroosmotic transport of acetaminophen in full thickness human skin and human stratum corneum. The flux of acetaminophen emerging from a pore in full thickness skin and stratum corneum is measured as a function of the iontophoretic current. It is found that the full thickness human skin gives rise to electroosmotic (EO) flow in shunt pathways, while human stratum corneum lacks this ability. It is concluded that EO flow arises in the epidermis or dermis layer of the skin.; Chapter 5 introduces a new SECM imaging technique that is useful for investigations of biological membranes. Reverse Imaging Mode (RIM) allows for investigations of membranes with the permeant molecule and the SECM tip located on the same side of the membrane.; In Chapter 6, the mathematical theory describing RIM is introduced and explained. The theoretical model is shown to agree with the experimental RIM concentration profiles of acetaminophen and FeCp₂TMA+ entering a mica/Nafion membrane under different values of iontophoretic current.; In Chapter 7, fluorescence microscopy is employed to study the in vivo transdermal transport pathways of rhodamine 6G in hairless mice. The mice are anesthetized and exposed to rhodamine 6G under diffusive and iontophoretic conditions. It was found that the rhodamine 6G penetrated to the lower dermis layer via hair follicles.