Soluble N-(2-hydroxypropyl) methacrylamide copolymers as a potential oral, controlled-release, drug delivery system. I. Bioadhesion to the rat intestine in vitro

Abstract

The interaction of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing pendent sugar residues or quaternary ammonium groups with adult rat intestine was examined in vitro. Copolymers containing sugar residues had a greater affinity for intestinal tissue than unmodified copolymer, but the cationic derivative displayed the greatest tissue association. The extent of tissue association was dependent upon the sugar residue present, and increased in the order fucose > mannose > galactose. Eversion of intestinal tissue caused an increase in the tissue association of copolymers containing galactose attached directly to the copolymer backbone, but had no effect if the sugar residue was attached via a glycylglycyl spacer. Measurement of HPMA-copolymer binding to specific regions of the intestine revealed that galactose-containing copolymers had slightly higher affinity for the duodenum/first- part jejunum, whereas fucose-containing copolymers adhered more to distal regions particularly the third-part jejunum. The cationic derivative bound strongly to all regions. The HPMA copolymers described here could be useful in oral delivery formulations, to slow gastrointestinal transit time of drug, and also facilitate binding to specific regions of the gastrointestinal tract, allowing site-specific drug delivery.