The parent project is devoted to the development of bioadhesive, biorecognizable anti-inflammatory polymer conjugates for the treatment of colon disease. This proposed FIRCA application extends these studies into the development of bioadhesive, biorecognizable anticancer polymer conjugates for the treatment of colorectal adenocarcinoma. These systems will be based on the concept of binding of N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymer-peanut agglutinin (PNA)-9- aminocamptothecin (9-AC) conjugates to diseased sites by specific PNA- glycoprotein interactions, and on the concept of site-specific release of 9-AC by microbial enzymes present only in the colon.
The aim i s to design efficient conjugates targetable directly to the cancer tissue. The application also proposes to study the relationship between the structure of the copolymer conjugates and 9-AC release in vitro and in vivo. Both rat and human tissues will be used, and the correlation between animal and human data will be established.