In vitro transscleral iontophoresis of high molecular weight neutral compounds

The aim of the work was to study in vitro, across porcine and human sclera, the effect of transscleral iontophoresis on the permeation of high molecular weight neutral dextrans, chosen as models of high molecular weight drugs. Iontophoretic (anodal and cathodal) and passive permeation experiments were performed through pig sclera using acetaminophen (MW = 151 Da) and labelled dextrans (MW between 4.4 kDa and 120 kDa) as neutral model compounds. Anodal iontophoresis of 120 kDa dextran was also performed on human sclera. Membrane charge was also determined at different pH values. Both human and pig sclera show a net negative charge at pH 7.4 and in the presence of current an electroosmotic convective solvent flow in the anode-to-cathode direction takes place. During anodal iontophoresis, the electroosmotic flow (whose entity resulted approximately 4 μl cm-2 h-1) was able to increase 2-6.5 times the transscleral flux of dextrans. Transscleral iontophoresis can be useful for enhancing the transport across the sclera of high molecular weight compounds, even though neutral. This result suggests a possible application of this technique for the non-invasive administration of new biotech drugs for the treatment of the posterior segment eye diseases. © 2008 Elsevier B.V. All rights reserved.