Chelating Polymers for Hereditary Hemochromatosis Treatment
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
32954629
DOI
10.1002/mabi.202000254
Knihovny.cz E-zdroje
- Klíčová slova
- SPECT, antioxidant, experimental therapy, hemochromatosis, iron metabolism, iron overload, maintenance therapy, polymeric chelator, preventive therapy, siderophore, uptake inhibitor,
- MeSH
- benzen chemie farmakologie MeSH
- chelátory železa chemie farmakologie MeSH
- fenantroliny chemie farmakologie MeSH
- gastrointestinální trakt účinky léků MeSH
- hemochromatóza diagnostické zobrazování farmakoterapie patologie MeSH
- lidé MeSH
- polymery chemie farmakologie MeSH
- teoretické modely * MeSH
- tomografie emisní počítačová MeSH
- železo metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 1,10-phenanthroline MeSH Prohlížeč
- benzen MeSH
- chelátory železa MeSH
- fenantroliny MeSH
- polymery MeSH
- železo MeSH
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.
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