Release of 5‐aminosalicylic acid from bioadhesive <i>N</i>‐(2‐hydroxypropyl)methacrylamide copolymers by azoreductases <i>in vitro</i>

Abstract

Abstract N ‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymers ( 11a, b ) containing side chains terminating in 5‐aminosalicylic acid (5‐ASA) and fucosylamine ( 10 ) were synthesized. A reactive polymeric precursor ( 9 ), a copolymer of HPMA ( 7 ) and N ‐methacryloylglycylglycine p ‐nitrophenyl ester ( 8 ), was consecutively aminolyzed with 5‐[4‐(2‐aminoethylcarbamoyl)phenylazo]‐salicylic acid ( 6 ) and fucosylamine ( 10 ). The latter renders the copolymers bioadhesive in the gastrointestinal tract. The release of 5‐ASA from 11a, b was studied in vitro by incubation with cell‐free extracts isolated from rat cecum, and factors influencing the degradation were determined. The rate of azo bond cleavage of 11a, b was similar to the rate of cleavage of low‐molecular‐weight substrates, methyl orange and compound 6 . Addition of benzyl viologen, a low potential electron carrier, increased the rate of cleavage. At optimal benzyl viologen and substrate concentration ratios, a zero order release was observed. At higher substrate concentration, the rate of 5‐ASA release decreased.