It was the aim of this study to investigate the permeation enhancing effect of thiolated polycarbophil on the cornea of rabbits in vitro. The proposed reaction mechanism involves the opening of the tight junctions in the corneal epithelium. The modification of polycarbophil was achieved via covalent attachment of L-cysteine mediated by a carbodiimide. Transcorneal permeation studies were performed in Ussing-type diffusion chambers. As model compounds, sodium fluorescein, as a marker for paracellular transport, and dexamethasone phosphate were used. To evaluate potential corneal damage the corneal hydration level of each cornea was determined. Polycarbophil-cysteine was found to increase the permeation of sodium fluorescein 2.2-fold and that of dexamethasone phosphate 2.4-fold in comparison to the unmodified polymer. The concentration of dexamethasone in the acceptor medium was 1.5-fold increased. As evidenced by the corneal hydration level, polycarbophil-cysteine did not damage the corneal tissues. Therefore, polycarbophil-cysteine conjugates seem to be promising excipients for ocular drug delivery systems where they might be used as safe permeation enhancers.
Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2588-2592, 2002