IDENTIFICATION OF THE PATHWAY OF IONTOPHORETIC DRUG-DELIVERY - LIGHT AND ULTRASTRUCTURAL STUDIES USING MERCURIC-CHLORIDE IN PIGS

Although electrically assisted transdermal drug delivery has recently achieved a great deal of research attention, the precise anatomical pa thway followed by these drugs through the stratum corneum has not been clearly defined. Pigs are an accepted model for studying iontophoreti c drug delivery in humans. The purpose of this investigation was to vi sualize the pathway of ion transport by ion-tophoresing mercuric chlor ide. Weanling Yorkshire swine were dosed with 7.4% mercuric chloride i n the positive electrode at a current density of 200 mu Amp/cm(2) appl ied for 1 hr. Biopsies were immediately taken, exposed to 25% ammonium sulfide vapor to precipitate and localize the mercury, fixed, and pro cessed for light and transmission electron microscopy. The presence of mercury, which appeared as a black precipitate, was confirmed using e nergy-dispersive X-ray microanalysis. Although some compound penetrate d the skin through appendageal pathways, the electron micrographs clea rly revealed that mercuric chloride traversed the intact stratum corne um via an intercellular route. Precipitate was also localized in the o uter membrane of the mitochondria in the viable epidermal cells, derma l fibroblasts, and capillaries, demonstrating transdermal delivery and systemic exposure to the mercury. These findings have implications fo r iontophoretic drug delivery, since they allow visualization of the f unctional ''pores'' predicted by mathematical models.