Chelating Polymers for Hereditary Hemochromatosis Treatment
| Autor: | Kristýna Kolouchová, Pavla Francová, Jiří Czernek, Ondřej Groborz, Petr Paral, Jan Kučka, Petr Štěpánek, Martin Hrubý, Pavel Švec, Jan Krijt, Vijay Madhav Miriyala, Radek Pohl, Jiří Beneš, Tomáš Heizer, Lenka Loukotová, Martin Báječný, Pavel Hobza, David Dunlop, Luděk Šefc, Lenka Poláková |
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| Rok vydání: | 2020 |
| Předmět: |
Siderophore
Polymers and Plastics Polymers Iron Bioengineering 02 engineering and technology Pharmacology Iron Chelating Agents 010402 general chemistry 01 natural sciences Biomaterials Pharmacokinetics In vivo Materials Chemistry medicine Humans Chelation Hemochromatosis Gastrointestinal tract Chemistry Benzene Models Theoretical 021001 nanoscience & nanotechnology medicine.disease 0104 chemical sciences Gastrointestinal Tract Hereditary hemochromatosis Toxicity 0210 nano-technology Phenanthrolines Tomography Emission-Computed Biotechnology |
| Zdroj: | Macromolecular Bioscience. 20:2000254 |
| ISSN: | 1616-5195 1616-5187 |
| DOI: | 10.1002/mabi.202000254 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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