1. Biopolymer strategy for the treatment of Wilson's disease.
- Author
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Vetrik M, Mattova J, Mackova H, Kucka J, Pouckova P, Kukackova O, Brus J, Eigner-Henke S, Sedlacek O, Sefc L, Stepanek P, and Hruby M
- Subjects
- Animals, Cellulose pharmacokinetics, Chitosan pharmacokinetics, Copper, Copper Radioisotopes administration & dosage, Copper Radioisotopes pharmacokinetics, Gastrointestinal Tract metabolism, Hepatolenticular Degeneration metabolism, Oxyquinoline pharmacokinetics, Rats, Wistar, Cellulose administration & dosage, Chitosan administration & dosage, Hepatolenticular Degeneration drug therapy, Oxyquinoline administration & dosage
- Abstract
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
64 CuCl2 solution together with the polymers with covalently bound 8-hydroxyquinoline through a gastric probe.64 Copper complex uptake from the gastrointestinal tract was significantly inhibited by both chelating polymers. With the modified polymers, the presence of64 Cu 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., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2018
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