Wilson's disease is a genetic disorder that causes excessive accumulation of copper in the body, leading to toxic damage, especially in the liver and nervous system. The current treatment cause burdensome side effects. We describe the use of chemically modified biopolymer carriers based on microcrystalline cellulose and chitosan containing the highly specific copper chelator 8-hydroxyquinoline as a new type of therapy for Wilson's disease. The chelators can scavenges copper ions released from food during digestion and copper ions present in secretions in the gastrointestinal tract. Because the chelator is covalently bound to indigestible biopolymer carriers (crosslinked chitosan or modified cellulose), it is not taken up by the gastrointestinal tract and it can be eliminated through the feces, avoiding unwanted side effects. This concept was tested on Wistar rats, which received a radioactive 64CuCl2 solution together with the polymers with covalently bound 8-hydroxyquinoline through a gastric probe. 64Copper complex uptake from the gastrointestinal tract was significantly inhibited by both chelating polymers. With the modified polymers, the presence of 64Cu was detected mostly in the gastrointestinal tract, not in the internal organs. These findings indicate modified cellulose and crosslinked chitosan, with covalently bound 8-hydroxyquinoline exhibited the potential to be excellent therapeutics for treating Wilson's disease.

Center for Advanced Preclinical Imaging 1st Faculty of Medicine Charles University Salmovská 3 120 00 Prague 2 Czech Republic

Institute of Biophysics and Informatics 1st Faculty of Medicine Charles University Salmovska 1 120 00 Prague 2 Czech Republic

Institute of Macromolecular Chemistry Czech Academy of Sciences Heyrovsky Sq 2 162 06 Prague 6 Czech Republic

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