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      Transdermal iontophoresis: modulation of electroosmosis by polypeptide.

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          Abstract

          The objective of this research was to further evaluate the relative importance of electrorepulsion and electroosmosis to the mechanism of enhanced transport across the skin during iontophoresis. Specifically, the impact of iontophoresing into the skin positively and negatively charged polypeptides (poly-L-lysines and poly-L-glutamic acids, respectively) on the membrane's permselectivity and hence on the quantity and direction of electroosmotic flow, was examined. Experiments were performed in vitro at pH 7.4 using conventional methodology; electroosmosis during the iontophoresis of the polypeptides into and across the skin was tracked in the usual way via the movement of the polar, uncharged, non-metabolizable marker, D-mannitol. Electrotransport of the cationic 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 with the molecular weight of the polypeptide employed (from 1 to 25 kilodaltons). Iontophoresis of the anionic poly-L-glutamic acids from the cathode provoked a slight increase in electroosmotic flow in the 'reverse' direction (i.e. from the receptor phase beneath the skin towards the cathode chamber located on the epidermal side of the membrane); this 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 leads 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 relatively poor iontophoretic permeability of these species (which becomes more and more evident with increasing molecular weight) results in a sufficiently important association of the polypeptide with the skin during the period of current passage. Much less significant effects are realized by the cathodal iontophoresis of poly-anions due to the difficulty of 'pushing' negative ions into an already negatively-charged membrane.

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          Author and article information

          Journal
          J Control Release
          Journal of controlled release : official journal of the Controlled Release Society
          0168-3659
          0168-3659
          Jan 02 1998
          : 50
          : 1-3
          Affiliations
          [1 ] Department of Biopharmaceutical Sciences, University of California, San Francisco 94143-0446, USA.
          Article
          S0168-3659(97)00150-8
          10.1016/S0168-3659(97)00150-8
          9685895
          90ed5e8a-d3fe-4bf7-b0c3-0e6d27b73f74
          History

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