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 colon ic mucosal lectins and on the concept of site-specific drug (5-aminosa licylic acid) release by the microbial azoreductase activity present i n the colon. A new 5-aminosalicylic acid-containing monomer was synthe sized and incorporated into the copolymer together with the fucosylami ne (bioadhesive moiety)-containing comonomer by radical copolymerizati on. The in vitro release rate of 5-ASA from HPMA copolymers by azoredu ctase activity in guinea pig cecum was approx. 2.5 times lower than fr om a low molecular weight analog. The azoreductase activities in cecum contents of guinea pig, rat, and rabbit as well as in human feces wer e 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 gu inea pig colon when compared to HPMA copolymer without fucosylamine mo ieties. The incorporation of 5-ASA-containing aromatic side-chains int o HPMA copolymers further increased their adherence probably by combin ation of nonspecific hydrophobic binding with specific recognition.