ROLE OF APPENDAGES IN SKIN RESISTANCE AND IONTOPHORETIC PEPTIDE FLUX - HUMAN VERSUS SNAKE SKIN

Purpose. 1. The assessment of the role of hair follicles and sweat gla nds in skin resistance and percutaneous iontophoretic flux of 9-desgly cinamide, 8-arginine vasopressin (DGAVP) by comparing two skin species : human stratum corneum which contained hair follicles, sweat and seba ceous glands, and shed snake skin which lacked all appendages. 2. The effect of 1-dodecylazacycloheptan-2-one (dodecyl-Azone, a lipid pertur bing agent) on the iontophoretic DGAVP flux. Methods. Iontophoresis in vitro was performed in a transport cell (0.79 cm(2) area available fo r percutaneous transport) by 8-hours application of a pulsed constant current of 100 Hz, 50% duty cycle and 0.26 mA.cm(-2) current density d elivered by a pair of Ag/AgCl electrodes, of which the anode was facin g the anatomical surface of the skin samples. Results. The initial res istances of human stratum corneum and shed snake skin samples were of the same order of magnitude (20-24 k Omega.cm(2)) and both skin specie s showed a comparable resistance-decrease profile during 8-hours ionto phoresis, indicating that the resistances were mainly determined by th e stratum corneum and not greatly influenced by the appendageal struct ures. The initial resistances of the skin samples pretreated with dode cyl-azone were less than 50% of the values of untreated samples. Becau se dodecylazone is known to perturb the ordering of the intercellular lipids, the effect of atone on the resistance confirms that the resist ance mainly resides within the intercellular lipids of the stratum cor neum. No correlation was found between the iontophoretic DGAVP-flux an d the conductance of human skin. For shed snake skin, however, a good correlation was found, indicating that the iontophoretic permeability of human skin;in vitro for a peptide such as DGAVP is, unlike shed sna ke skin, not related to its overall permeability to ions. While the in itial resistances of both human and snake skin were in the same order of magnitude and showed the same declining profile during iontophoresi s, the steady state iontophoretic DGAVP flux across human stratum corn eum was approximately 140 times larger than through shed snake skin. T hese findings suggest that small ions follow pathways common to both s kin types, presumably the intercellular route, while the peptide on th e other hand is transported differently: across snake skin presumably along intercellular pathways only, but across human stratum corneum al ong additional pathways (most likely of appendageal origin) as well. T his interpretation is supported by the observations made of the effect s of dodecyl-azone on DGAVP-iontophoresis. Pretreatment with dodecylaz one did not significantly change steady state fluxes and lag times of DGAVP-iontophoresis across human stratum corneum, but resulted in a si gnificant 3-fold lag time decrease and a 3-fold flux increase of DGAVP -iontophoresis across snake skin. Conclusions. The results of these in vitro studies emphasize the importance of the appendageal pathway for iontophoretic peptide transport across human stratum corneum.