Chelating polymers for hereditary hemochromatosis treatment

0536333 - ÚMCH 2021 RIV DE eng J - Journal Article
Groborz, Ondřej - Poláková, Lenka - Kolouchová, Kristýna - Švec, Pavel - Loukotová, Lenka - Miriyala, Vijay Madhav - Francová, P. - Kučka, Jan - Krijt, J. - Páral, P. - Báječný, M. - Heizer, T. - Pohl, Radek - Dunlop, David - Czernek, Jiří - Šefc, L. - Beneš, J. - Štěpánek, Petr - Hobza, Pavel - Hrubý, Martin
Chelating polymers for hereditary hemochromatosis treatment.
Macromolecular Bioscience. Roč. 20, č. 12 (2020), s. 1-16, č. článku 2000254. ISSN 1616-5187. E-ISSN 1616-5195
R&D Projects: GA ČR(CZ) GA19-01438S; GA ČR(CZ) GX19-27454X; GA MŠMT(CZ) LO1507
Research Infrastructure: Czech-BioImaging II - 90129; CESNET II - 90042; CERIT-SC - 90085
Institutional support: RVO:61389013 ; RVO:61388963
Keywords : antioxidant * experimental therapy * hemochromatosis
OECD category: Polymer science; Inorganic and nuclear chemistry (UOCHB-X)
Impact factor: 4.979, year: 2020
Method of publishing: Limited access
https://onlinelibrary.wiley.com/doi/10.1002/mabi.202000254

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 125I‐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.
Permanent Link: http://hdl.handle.net/11104/0314360