Synthesis of bioadhesive lectin-HPMA copolymer- cyclosporin conjugates

An amino group containing cyclosporin A (CsA) derivative has been synthesiz ed and conjugated to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer via an aromatic azo bond, which can be specifically cleaved by azoreductase ac tivity in colon to release the drug for the treatment of colon diseases. Le ctins, peanut (Arachis hypogea) agglutinin (PNA) and wheat germ agglutinin (WC;A), have been conjugated to HPMA copolymer-CsA derivative conjugates (P CsA), respectively, to give bioadhesive conjugates. The PNA and WGA are the targeting proteins that can bind to diseased colon tissue and healthy tiss ue, respectively. There were on average four P(CsA) copolymer chains attach ed on one WGA molecule with a drug content of 16.0 wt % and five P(CsA) cop olymer chains attached on one PNA molecule with a drug content of 11.5 wt % . The incubation of a P(CsA) copolymer with the rat cecal contents resulted in the cleavage of the azo bond and release of the cyclosporin derivative. The biological evaluation of the conjugates is under way.