title: Synthesis of bioadhesive lectin-HPMA copolymer-cyclosporin conjugates.
abstract: An amino group containing cyclosporin A (CsA) derivative has been synthesized and conjugated to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer via an aromatic azo bond, which can be specifically cleaved by azoreductase activity in colon to release the drug for the treatment of colon diseases. Lectins, peanut (Arachis hypogea) agglutinin (PNA) and wheat germ agglutinin (WGA), have been conjugated to HPMA copolymer-CsA derivative conjugates (PCsA), respectively, to give bioadhesive conjugates. The PNA and WGA are the targeting proteins that can bind to diseased colon tissue and healthy tissue, respectively. There were on average four P(CsA) copolymer chains attached on one WGA molecule with a drug content of 16.0 wt % and five P(CsA) copolymer 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.
authors.affiliation: Departments of Pharmaceutics and Pharmaceutical Chemistry/CCCD, and Bioengineering, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Z R
authors.initials: ZR
authors.lastname: Lu
authors.forename: S Q
authors.initials: SQ
authors.lastname: Gao
authors.forename: P
authors.initials: P
authors.lastname: Kopecková
authors.forename: J
authors.initials: J
authors.lastname: Kopecek
mesh_terms: D000269:Adhesives / Q000138:chemical synthesis* / Q000378:metabolism; D000818:Animals; D002432:Cecum / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D003524:Cyclosporins / Q000138:chemical synthesis* / Q000378:metabolism; D016503:Drug Delivery Systems; D004355:Drug Stability; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D008689:Methacrylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D019887:Peanut Agglutinin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D014909:Wheat Germ Agglutinins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000269:Adhesives; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D008689:Methacrylates; D019887:Peanut Agglutinin; D014909:Wheat Germ Agglutinins; D016572:Cyclosporine; C032802:hydroxypropyl methacrylate