BIOADHESIVE N-(2-HYDROXYPROPYL) METHACRYLAMIDE COPOLYMERS FOR COLON-SPECIFIC DRUG-DELIVERY

N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers were evaluated as colon-specific drug carriers. Their design was based on the concept of site-specific binding of carbohydrate moieties complementary to colonic mucosal lectins and on the concept of site-specific drug (5-aminosalicylic acid) release by the microbial azoreductase activity present in the colon. A new 5-aminosalicylic acid-containing monomer was synthesized and incorporated into the copolymer together with the fucosylamine (bioadhesive moiety)-containing comonomer by radical copolymerization. The in vitro release rate of 5-ASA from HPMA copolymers by azoreductase activity in guinea pig cecum was approx. 2.5 times lower than from a low molecular weight analog. The azoreductase activities in cecum contents of guinea pig, rat, and rabbit as well as in human feces were determined. The relative activities for rat:guinea pig:human:rabbit were 100:65:50:28. Both in vitro and in vivo HPMA copolymer-containing sidechains terminated in fucosylamine showed a higher adherence to guinea pig colon when compared to HPMA copolymer without fucosylamine moieties. The incorporation of 5-ASA-containing aromatic side-chains into HPMA copolymers further increased their adherence probably by combination of nonspecific hydrophobic binding with specific recognition.