Polymeric nanocarriers for the treatment of systemic iron overload
department or school: Chemistry, Department of
department or school: Medicine, Faculty of
department or school: Pathology and Laboratory Medicine, Department of
department or school: Science, Faculty of
data provider: DSpace
identifier citation: Molecular and Cellular Therapies. 2015 Mar 24;3(1):3
contributor: University of British Columbia. Centre for Blood Research
rights copyright: Hamilton and Kizhakkedathu; licensee BioMed Central.
creator: Hamilton, Jasmine L.
creator: Kizhakkedathu, Jayachandran N.
issued: 2015-11-05T03:24:02
issued: 2015-03-24
description: Desferrioxamine (DFO), deferiprone (L1) and desferasirox (ICL-670) are clinically approved iron chelators used to treat secondary iron overload. Although iron chelators have been utilized since the 1960s and there has been much improvement in available therapy, there is still the need for new drug candidates due to limited long-term efficacy and drug toxicity. Moreover, all currently approved iron chelators are of low molecular weight (MW) (<600 Da) and the objectives reported for the “ideal” chelator of low MW, including possessing the ability to promote iron excretion without causing toxic side effects, has proven difficult to realize in practice. With prolonged iron chelator use, patients may develop toxicities or become insensitive. In contrast, the limited research that has been geared towards developing higher MW, polymeric, long circulating iron chelators has shown promise. The inherent potential of polymeric iron chelators toward longer plasma half-lives and reduction in toxicity provides optimism and may be a significant addition to the currently available low MW iron chelators. This article reviews knowledge pertaining to this theme, highlights some unique advantages that these nanomedicines have in treating systemic iron overload as well as their potential utility in the treatment of other disease states.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/55207
note: REVIEWPolymeric nanocarriers for1,2(ICveorhenclize ls storcome by evolving to conserve iron [1-3]. Organisms haveacquired highly organized mechanisms of iron acqui-and approximately 1–2 mg of iron is lost daily due tothe sloughing off of epithelial cells, secretions from theHamilton and Kizhakkedathu Molecular and Cellular Therapies (2015) 3:3 DOI 10.1186/s40591-015-0039-1binding proteins which ensure that it is unable to cause2Department of Chemistry, University of British Columbia, 2350 HealthSciences Mall, Vancouver, BC V6T 1Z3, Canadasition, transport and storage; microorganisms use lowmolecular weight (MW) high affinity iron ligands orsiderophores, while more complex life forms like mam-mals use specialized storage and transport proteins [3].skin and gut, and small losses of blood from the gastro-intestinal tract [2,3]. This indicates the conservative na-ture of iron metabolism and recycling. The process ofiron recycling and metabolism is schematically demon-strated in Figure 1.Under normal physiological conditions, iron is com-plexed with proteins like transferrin (Tf) or other iron* Correspondence: jay@pathology.ubc.ca1The Centre for Blood Research, Department of Pathology and LaboratoryMedicine, Vancouver, BC V6T 1Z3, Canadasome unique advantages that these nanomedicines have in treating systemic iron overload as well as their potentialutility in the treatment of other disease states.Keywords: Iron overload, Iron chelation therapy, Iron chelators, Desferrioxamine, Deferiprone, Desferasirox,Nanomaterials, Polymeric chelatorsReviewIronIron is essential for oxygen transport, DNA synthesisand energy metabolism [1]. Thus, it is life sustaining invirtually all living organisms. The usefulness of iron re-sults from its ability to cycle between its ferrous (Fe2+)and ferric (Fe3+) forms in oxidation and reduction reac-tions [1,2]. Although iron is abundant in the earth’scrust, Fe2+ is highly toxic, while Fe3+ is insoluble inaqueous solution at physiological pH, rende…
has type: Article
is shown at: 10.14288/1.0215963
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: BioMed Central
publisher DOI: 10.1186/s40591-015-0039-1
rights: Attribution 4.0 International (CC BY 4.0)
rights URI: http://creativecommons.org/licenses/by/4.0/
scholar level: Faculty
subject: Iron overload
subject: Iron chelation therapy
subject: Iron chelators
subject: Desferrioxamine
subject: Deferiprone
subject: Desferasirox
subject: Nanomaterials
subject: Polymeric chelators
type: Text
identifier URI: http://hdl.handle.net/2429/55207