New types of synthetic water soluble polymeric systems for the treatme
nt of colon disease are described. These systems are based on the conc
ept of binding of polymeric carriers containing carbohydrate moieties
complementary to colonic mucosal lectins and on the concept of site-sp
ecific release of drug (5-aminosalicylic acid) from the polymeric carr
ier by the degrading action of microbial enzymes present in the colon.
New synthetic pathways have been developed for the synthesis of N-(2-
hydroxypropyl)methacrylamide copolymers containing high amounts of bot
h the bioadhesive moiety (fucosylamine) and 5-aminosalicylic acid. Fuc
osylamine containing copolymers bind to the colonic mucosa of guinea p
igs. The higher the content of fucosylamine, the higher the binding. T
he binding can be inhibited by unbound fucose indicating the presence
of specific lectin-like structures in the guinea pig colon. New biodeg
radable hydrogels containing both acidic comonomers and enzymatically
degradable azoaromatic crosslinks were synthesized. These hydrogels ar
e suitable for site-specific delivery of peptides (proteins) into the
colon. In the low pH range of the stomach, the gels have a low equilib
rium degree of swelling and the drug is protected against digestion by
enzymes. The degree of swelling increases as the hydrogel passes down
the gastrointestinal tract due to increased pH. In colon, the hydroge
ls have reached a degree of swelling that makes the crosslinks accessi
ble to azoreductases and mediators. The rate of degradation depends on
the structure of the hydrogels. Total dissolution in vivo can be achi
eved in less than 48 h. Brush border membrane and luminal enzymes were
isolated from guinea pig small intestine and colon. Their enzymatic a
ctivity towards insulin and insulin B-chain was compared. It was shown
that the extent of peptide degradation is substantially lower with co
lonic enzymes when compared to those isolated from the small intestine
.