Chelating polymeric beads as potential therapeutics for Wilson’s disease

Mattová, J.; Poučková, P.; Kučka, Jan; Škodová, Michaela; Vetrík, Miroslav; Štěpánek, Petr; Urbánek, P.; Petřík, M.; Nový, Z.; Hrubý, Martin

doi:https://dx.doi.org/10.1016/j.ejps.2014.05.002

Number of the records: 1

Chelating polymeric beads as potential therapeutics for Wilson’s disease

1.

SYSNO ASEP	0431233
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Chelating polymeric beads as potential therapeutics for Wilson’s disease
Author(s)	Mattová, J. (CZ) Poučková, P. (CZ) Kučka, Jan (UMCH-V)_{RID, ORCID} Škodová, Michaela (UMCH-V)_RID Vetrík, Miroslav (UMCH-V)_{RID, ORCID} Štěpánek, Petr (UMCH-V)_{RID, ORCID} Urbánek, P. (CZ) Petřík, M. (CZ) Nový, Z. (CZ) Hrubý, Martin (UMCH-V)_{RID, ORCID}
Source Title	European Journal of Pharmaceutical Sciences. - : Elsevier - ISSN 0928-0987 Roč. 62, 1 October (2014), s. 1-7
Number of pages	7 s.
Language	eng - English
Country	NL - Netherlands
Keywords	Wilson’s disease ; polymer beads ; chelators
Subject RIV	CA - Inorganic Chemistry
R&D Projects	GAP304/12/0950 GA ČR - Czech Science Foundation (CSF)
	GA13-08336S GA ČR - Czech Science Foundation (CSF)
	FR-TI4/625 GA MPO - Ministry of Industry and Trade (MPO)
Institutional support	UMCH-V - RVO:61389013
UT WOS	000340301500001
EID SCOPUS	84901446565
DOI	10.1016/j.ejps.2014.05.002
Annotation	Wilson’s disease is a genetic disorder caused by a malfunction of ATPase 7B that leads to high accumulation of copper in the organism and consequent toxic effects. We propose a gentle therapy to eliminate the excessive copper content with oral administration of insoluble non-resorbable polymer sorbents containing selective chelating groups for copper(II). Polymeric beads with the chelating agents triethylenetetramine, N,N-di(2-pyridylmethyl)amine, and 8-hydroxyquinoline (8HQB) were investigated. In a preliminary copper uptake experiment, we found that 8HQB significantly reduced copper uptake (using copper-64 as a radiotracer) after oral administration in Wistar rats. Furthermore, we measured organ radioactivity in rats to demonstrate that 8HQB radiolabelled with iodine-125 is not absorbed from the gastrointestinal tract after oral administration. Non-resorbability and the blockade of copper uptake were also confirmed with small animal imaging (PET/CT) in mice. In a long-term experiment with Wistar rats fed a diet containing the polymers, we have found that there were no signs of polymer toxicity and the addition of polymers to the diet led to a significant reduction in the copper contents in the kidneys, brains, and livers of the rats. We have shown that polymers containing specific ligands could potentially be novel therapeutics for Wilson’s disease.
Workplace	Institute of Macromolecular Chemistry
Contact	Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358
Year of Publishing	2015

Number of the records: 1