Combating Iron Overload: A Case for Deferoxamine-Based Nanochelators

Jones, Gregory; Goswami, Sumanta; Kang, Homan; Choi, Hak; Kim, Jonghan

doi:10.2217/nnm-2020-0038

Cited by 28 publications

(21 citation statements)

References 79 publications

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“…DFO is not administered orally due to its poor oral absorption capacity and pharmacokinetics. It is recommended to only administer intramuscularly and with continuous intravenous infusions ( Jones et al, 2020 Jun ). DFO is transported away from the plasma readily with a biological half-life of 5–10 minutes, which prompted extended subcutaneous infusion ( Yu et al, 2020 Apr ).…”

Section: Iron Chelation Therapymentioning

confidence: 99%

Therapeutic potential of induced iron depletion using iron chelators in Covid-19

Naseef

Elayadeth-Meethal

et al. 2022

Saudi Journal of Biological Sciences

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Ferritin, which includes twenty-four light and heavy chains in varying proportions in different tissues, is primarily responsible for maintaining the body's iron metabolism. Its normal value is between 10 and 200 ngmL -1 in men and between 30-300 ngmL -1 in women. Iron is delivered to the tissue via them, and they act as immunomodulators, signaling molecules, and inflammatory markers. When ferritin level exceeds 1000 µgL -1 , the patient is categorized as having hyperferritinemia. Iron chelators such as deferiprone, deferirox, and deferoxamine are currently FDA approved to treat iron overload. The inflammation cascade and poor prognosis of COVID-19 may be attributed to high ferritin levels. Critically ill patients can benefit from deferasirox, an iron chelator administered orally at 20-40 mgkg -1 once daily, as well as intravenous deferoxamine at 1000 mg initially followed by 500 mg every 4 to 12 hours. It can be combined with monoclonal antibodies, antioxidants, corticosteroids, and lactoferrin to make iron chelation therapy effective for COVID-19 victims. In this article, we analyze the antiviral and antifibrotic activity of iron chelators, thereby promoting iron depletion therapy as a potentially innovative treatment strategy for COVID-19.

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Section: Iron Chelation Therapymentioning

confidence: 99%

Therapeutic potential of induced iron depletion using iron chelators in Covid-19

Naseef

Elayadeth-Meethal

et al. 2022

Saudi Journal of Biological Sciences

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“…For alginate, however, its calcium-chelating ability connected with gelation can be an issue. Analogously, deferoxamine was conjugated to enzymatically activable polyrotaxane to promote polymer carrier degradation after it fulfills its task [102,103]. Alternatively, enzymatically degradable hydroxyethylated starch can be employed [104,105].…”

Section: Polymers and Nanospecies With Bound Chelators To Be Applied Parenterallymentioning

confidence: 99%

“…Consistently with this, trans-chelation rate is less dependent on whether the trans-chelator is polymer-bound for low-molecular-weight iron-donor species. Nevertheless, polymer chelators are efficient even in vitro on cells and in vivo on animal models [96][97][98][99][100][101][102][103][104][105][106].…”

Section: Polymers and Nanospecies With Bound Chelators To Be Applied Parenterallymentioning

confidence: 99%

“…Dendrimers are highly defined hierarchical structures, much more regular than structurally somehow-related hyperbranched polymers, with the hydrodynamic radius usually below the renal threshold and therefore with renal elimination as the primary way of elimination. Iron-chelating dendrimers were synthesized [102,115] with deferoxamine iron-chelating moieties. Nanogels are gel-structured nanoparticles and with appropriate iron-chelating moieties [116][117][118][119]; however, due to their larger size, they must be biodegradable to allow elimination.…”

Section: Polymers and Nanospecies With Bound Chelators To Be Applied Parenterallymentioning

confidence: 99%

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Chelators for Treatment of Iron and Copper Overload: Shift from Low-Molecular-Weight Compounds to Polymers

et al. 2021

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Iron and copper are essential micronutrients needed for the proper function of every cell. However, in excessive amounts, these elements are toxic, as they may cause oxidative stress, resulting in damage to the liver and other organs. This may happen due to poisoning, as a side effect of thalassemia infusion therapy or due to hereditary diseases hemochromatosis or Wilson’s disease. The current golden standard of therapy of iron and copper overload is the use of low-molecular-weight chelators of these elements. However, these agents suffer from severe side effects, are often expensive and possess unfavorable pharmacokinetics, thus limiting the usability of such therapy. The emerging concepts are polymer-supported iron- and copper-chelating therapeutics, either for parenteral or oral use, which shows vivid potential to keep the therapeutic efficacy of low-molecular-weight agents, while avoiding their drawbacks, especially their side effects. Critical evaluation of this new perspective polymer approach is the purpose of this review article.

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“…One of the most severe effects of iron overload is the capacity of the Fe(II)/Fe(III) redox cycle to produce dangerous hydroxyl free radicals; on the contrary, low iron(III) levels reduce its concentration in the hemoglobin and generate pathologies such as thrombocytosis or hypoxia [4]. Iron-chelation therapy is commonly used in people affected by iron overload to maintain a correct Fe(III) level in the organism [5], but the long-term use of iron(III) chelators can lead to severe side effects [6,7].…”

Section: Introductionmentioning

confidence: 99%

DFO@EVOH and 3,4-HP@EVOH: Towards New Polymeric Sorbents for Iron(III)

et al. 2020

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The paper presents the synthesis and preliminary characterization of two novel solid-phase sorbents for iron(III), resulting from the functionalization of ethylene-vinyl alcohol copolymer (EVOH) with deferoxamine, DFO (DFO@EVOH), and a novel tripodal 3-hydroxy-4-pyridinone, named 3,4-HP (3,4-HP@EVOH). DFO and 3,4-HP have been covalently bonded to EVOH, using carbonyldiimidazole as a coupling agent. Before their use as Fe(III) sorbents, they were warm-pressed to obtain a thin film. Polymers have been characterized by conventional physico-chemical techniques; furthermore, the sorption properties towards Fe(III) were investigated. The physico-chemical characterization of the new solid-state devices demonstrates the effective linkage of the two receptors on the polymeric support. Despite a relatively low sorption capacity for both materials, the stoichiometry and the complexation constants of Fe(III)/DFO@EVOH and Fe(III)/3,4-HP@EVOH are in pretty good agreement with those obtained for the same ligands in aqueous solutions.

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Combating Iron Overload: A Case for Deferoxamine-Based Nanochelators

Cited by 28 publications

References 79 publications

Therapeutic potential of induced iron depletion using iron chelators in Covid-19

Therapeutic potential of induced iron depletion using iron chelators in Covid-19

Chelators for Treatment of Iron and Copper Overload: Shift from Low-Molecular-Weight Compounds to Polymers

DFO@EVOH and 3,4-HP@EVOH: Towards New Polymeric Sorbents for Iron(III)

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