Nonabsorbable Iron(III) binding polymers: Synthesis and evaluation of the chelating properties

被引:3
|
作者
Ghisalberti, Carlo Angelo [1 ,2 ]
Falletta, Ermelinda [3 ]
Lammi, Carmen [4 ]
Facchetti, Giorgio [4 ]
Bucci, Raffaella [4 ]
Erba, Emanuela [4 ]
Pellegrino, Sara [4 ]
机构
[1] Univ Milan, SCIBIS Dipartimento Sci Salute, Milan, Italy
[2] Tixupharma, Via Luigi Mangiagalli 31, Milan, Italy
[3] Univ Milan, Dipartimento Chim, Milan, Italy
[4] Univ Milan, DISFARM Dipartimento Sci Farmaceut, Milan, Italy
关键词
Fe(III) binding polymers; N-Alkyl-3-hydroxypyridin-4-one; Polyethyleneimine; Carboxymethyl cellulose; Iron overload; IRON; COMPLEXES; HYDROXYPYRIDINONES;
D O I
10.1016/j.polymertesting.2020.106693
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Iron is a key micronutrient essential for many biological events. While iron deficiency can lead to anemia, supplementation with oral iron often ends up with enteral iron overload, a critical gastrointestinal (GI) burden linked to the increased risk of dysbiosis, infections and often associated with colorectal cancer. Iron chelation therapy is clinically used to reduce pathological systemic iron overload by established low molecular weight iron chelators. As drawbacks, these drugs present low pharmacokinetic profiles and several toxicities, leading to relatively high rates of adverse effects. To overcome these issues, the prevention of iron accumulation in the GI tract by non-absorbable iron binding polymers could represent an alternative still underexploited approach. Here, we present the development of a series of insoluble polymeric Fe(III) chelators. These innovative compounds have been obtained by the conjugation of 3-hydroxypyridin-4-one Fe(III) chelating moiety with branched Polyethyleneimine (PEI) and Carboxymethyl cellulose (CMC). In vitro binding studies indicated that the Fe(III) chelating capacity depends on the nature of the polymer. In particular, PEI derivatives possess higher selectivity toward Fe(III) in simulated intestinal fluid preserving the integrity of intestinal enterocytes, representing thus promising compounds in the development of iron chelators.
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页数:7
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