Abstract 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.

中文翻译：

---

不可吸收的铁 (III) 结合聚合物：螯合特性的合成和评估

摘要 铁是许多生物事件必不可少的关键微量营养素。虽然缺铁会导致贫血，但补充口服铁剂通常会导致肠内铁过载，这是一种严重的胃肠 (GI) 负担，与生态失调、感染的风险增加有关，并且通常与结直肠癌有关。铁螯合疗法在临床上用于通过已建立的低分子量铁螯合剂来减少病理性全身铁过载。作为缺点，这些药物具有较低的药代动力学特征和多种毒性，导致不良反应发生率相对较高。为了克服这些问题，通过不可吸收的铁结合聚合物防止铁在胃肠道中积累可能代表了一种尚未充分利用的替代方法。这里，我们介绍了一系列不溶性聚合 Fe(III) 螯合剂的开发。这些创新化合物是通过 3-hydroxypyridin-4-one Fe(III) 螯合部分与支化聚乙烯亚胺 (PEI) 和羧甲基纤维素 (CMC) 共轭获得的。体外结合研究表明，Fe(III) 螯合能力取决于聚合物的性质。特别是，PEI 衍生物对模拟肠液中的 Fe(III) 具有更高的选择性，可保持肠细胞的完整性，因此代表了开发铁螯合剂的有前途的化合物。体外结合研究表明，Fe(III) 螯合能力取决于聚合物的性质。特别是，PEI 衍生物对模拟肠液中的 Fe(III) 具有更高的选择性，可保持肠细胞的完整性，因此代表了开发铁螯合剂的有前途的化合物。体外结合研究表明，Fe(III) 螯合能力取决于聚合物的性质。特别是，PEI 衍生物对模拟肠液中的 Fe(III) 具有更高的选择性，可保持肠细胞的完整性，因此代表了开发铁螯合剂的有前途的化合物。