CONVECTIVE SOLVENT FLOW ACROSS THE SKIN DURING IONTOPHORESIS

Enhanced flux of neutral solutes during transdermal iontophoresis is a ttributed largely to electroosmotic volume flow. In this study, the io ntophoretic fluxes of tritiated water ((H2O)-H-3) and C-14-labeled man nitol through hairless mouse skin (HMS) were determined. The following questions were addressed: (i) What is the variability of water flux d uring iontophoresis? (ii) To what extent is the iontophoretic flux of a neutral solute correlated with water flux? (iii) Does the intrinsic permeability of the skin to neutral solutes change following iontophor esis? (iv) What is the effect of low pH on electroosmotic volume flow? and (v) Does the skin remain permselective after removal of the strat um corneum? Transport of both water and mannitol reached steady-state levels during 10 hr of constant-current iontophoresis (0.36 mA/cm2). A nodal fluxes exceeded cathodal values. Cathodal mannitol flux was reta rded, relative to passive transport, by net volume flow in the opposit e direction, such that transport of this molecule increased significan tly after the termination of current passage. Anodal equivalent volume flows for water and mannitol, respectively, were 2.7 (+/-1.3) and 1.2 3 (+/-0.59) muL/hr cm2, indicating that only approximately 50% of the water flux participated in the electroosmosis of mannitol. The passive permeability of water and mannitol after 10 hr of iontophoresis was, respectively, 6 and 30 times greater than the pretreatment values. At pH 7, the cationic permselectivity of HMS was marginal [the Na+ transp ort number (t(Na+)) was determined to be 0.46] and less than that repo rted for human skin. Lowering the pH values of the solutions on either side of the skin to slightly less than 4 reversed the direction of ne t volume flow; cathodal flux was greater than anodal flux. When the do nor solution was at pH 3.8 and the receptor was pH 7.4, the flux profi le was complicated and net volume flow was not obvious. Finally, it wa s found that electroosmosis from anode to cathode was retained even fo llowing removal of the stratum corneum by tape-stripping.