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Chelating Polymers for Hereditary Hemochromatosis Treatment
Author(s) -
Groborz Ondřej,
Poláková Lenka,
Kolouchová Kristýna,
Švec Pavel,
Loukotová Lenka,
Miriyala Vijay Madhav,
Francová Pavla,
Kučka Jan,
Krijt Jan,
Páral Petr,
Báječný Martin,
Heizer Tomáš,
Pohl Radek,
Dunlop David,
Czernek Jiří,
Šefc Luděk,
Beneš Jiří,
Štěpánek Petr,
Hobza Pavel,
Hrubý Martin
Publication year - 2020
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.202000254
Subject(s) - hemochromatosis , gastrointestinal tract , chelation , biodistribution , in vivo , chemistry , polymer , chelation therapy , pharmacology , in vitro , medicine , biochemistry , organic chemistry , biology , microbiology and biotechnology
Hemochromatosis (iron overload) encompasses a group of diseases that are characterized by a toxic hyperaccumulation of iron in parenchymal organs. Currently, only few treatments for this disease have been approved; however, all these treatments possess severe side effects. In this study, a paradigm for hemochromatosis maintenance/preventive therapy is investigated: polymers with negligible systemic biological availability form stable complexes with iron ions in the gastrointestinal tract, which reduces the biological availability of iron. Macroporous polymer beads are synthesized with three different iron‐chelating moieties (benzene‐1,2‐diol, benzene‐1,2,3‐triol, and 1,10‐phenanthroline). The polymers rapidly chelate iron ions from aqueous solutions in vitro in the course of minutes, and are noncytotoxic and nonprooxidant. Moreover, the in vivo biodistribution and pharmacokinetics show a negligible uptake from the gastrointestinal tract (using 125 I‐labeled polymer and single photon emission computed tomography/computed tomography), which generally prevents them from having systemic side effects. The therapeutic efficacy of the prepared polymers is successfully tested in vivo, and exhibits a significant inhibition of iron uptake from the gastrointestinal tract without any noticeable signs of toxicity. Furthermore, an in silico method is developed for the prediction of chelator selectivity. Therefore, this paradigm can be applied to the next‐generation maintenance/preventive treatment for hemochromatosis and/or other diseases of similar pathophysiology.