TRANSDERMAL IONTOPHORESIS - MODULATION OF ELECTROOSMOSIS BY POLYPEPTIDES

The objective of this research was to further evaluate the relative im portance of electrorepulsion and electroosmosis to the mechanism of en hanced transport across the skin during iontophoresis. Specifically, t he impact of iontophoresing into the skin positively and negatively ch arged polypeptides (poly-L-lysines and poly-L-glutamic acids, respecti vely) on the membrane's permselectivity, and hence on the quantity and direction of electroosmotic flow, was examined. Experiments were perf ormed in vitro at pH 7.4 using conventional methodology; electroosmosi s during the iontophoresis of the polypeptides into and across the ski n was tracked in the usual way via the movement of the polar, uncharge d, non-metabolizable marker, D-mannitol. Electrotransport of the catio nic polypeptides attenuated electroosmotic flow in the normal anode-to -cathode direction; the degree of inhibition was correlated both with the initial concentration of poly-L-lysine in the anodal chamber and w ith the molecular weight of the polypeptide employed (from 1 to 25 Kil odaltons). Iontophoresis of the anionic poly-L-glutamic acids from the cathode provoked a slight increase in electroosmotic flow in the 'rev erse' direction (i.e. from the receptor phase beneath the skin towards the cathode chamber located on the epidermal side of the membrane); t his effect, however, was much less dramatic than that produced in the opposite sense by the cationic polypeptides. The results suggest that driving large positively-charged polypeptide molecules into the skin l eads to neutralization of the membrane's negativity, a subsequent loss of permselectivity and a concomitant attenuation of electroosmosis in the conventional anode-to-cathode direction. Presumably, the relative ly poor iontophoretic permeability of these species (which becomes mor e and more evident with increasing molecular weight) results in a suff iciently important association of the polypeptide with the skin during the period of current passage. Much less significant effects ate real ized by the cathodal iontophoresis of poly-anions due to the difficult y of 'pushing' negative ions into an already negatively-charged membra ne. (C) 1998 Elsevier Science B.V.