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Feb 24, 2016 - Aceruloplasminemia, and Transfusional Siderosis. Iron in free form provokes the production of reactive oxygen species (ROS) via Fenton ...
Editorial

Kenkyu Journal of Medical Science & Clinical Research

Open Access

Citation: Obulesu M (2016) Iron Chelation Therapy. KJ Medscicr 1: 100101

Iron Chelation Therapy Obulesu M Materials Science, University of Tsukuba, Japan *

Corresponding Author: Obulesu M, Materials Science, University of Tsukuba, Japan, e-mail;

[email protected]

1. Introduction Iron plays a pivotal role in human physiology by

Biomedical field. Although a few nanoparticles used

serving multifarious functions such as cofactor in a

for metal overload diseases, studies on polymer

few enzymes, transport of hemoglobin etc. However,

conjugated iron chelator are significantly less [1,2].

its overload leads to dreadful diseases such as

Synthesized starch conjugated desferrioxamine which

Alzheimer’s

Hemochromatosis,

showed better chelation efficacy and entered phase 1b

Aceruloplasminemia, and Transfusional Siderosis.

clinical trials several years ago. However, it has been

Iron in free form provokes the production of reactive

found to induce urticarial reactions in patients and

oxygen species (ROS) via Fenton reaction. Therefore,

discouraged at a later date. In another study dendrimer

scavenging the excess metal is of considerable

conjugated

importance in biomedical field.

improvement in therapeutic properties by chelating

disease,

desferrioxamine

showed

significant

iron. In this study, initially hyperbranched glycerol

2. Chelation Therapy

scaffold was prepared and several molecules of

Currently, chelation therapy is widely used to

desferrioxamine were covalently conjugated to it.

overcome the iron intoxication.

Long systemic circulation of the dendrimer conjugated

A few Food and

Drug Administration (FDA) approved drugs currently

chelator

was

observed

resulting

in

enhanced

in use show better chelation.

Desferrioxamine,

therapeutic property. However, in HPG conjugated

Deferasirox and Deferiprone are some of the FDA

DFO study optimization and biodistribution of the

approved drugs to circumvent the iron overload.

molecules is yet to be determined.

Despite the interesting metal chelation activity exerted by these chelators, their systemic toxicity, rapid

Liu’s

study

of

elimination from systemic circulation greatly impede

nanoparticle showed some promise in reducing the

their success.

iron overload in brain tissue. They used 2-Methyl-N(2′-aminoethyl

To address the issues associated with low molecular weight compounds a potential polymer conjugated iron chelator, which successfully removes free iron

Volume 1, Issue 1 -KJMSCR-100101

or

iron

chelators

to

3′-aminopropyl)-3-hydroxyl-4-

pyridinone (MAEHP), 2-Methyl (or Ethyl)-N-(2′-

3. Nanotechnology for Chelators

from the cells, is of utmost importance in the

conjugating

hydroxyethoxy)

methyl-3-hydroxyl-4-pyridinone

(MHEMHP). Monodispersed polystyrene particles with carboxyl groups on the surface were used to conjugate MAEHP chelators, each of which contained

www.kenkyuonline.org

Received: February 24, 2016; Accepted: February, 2016; Published: February, 2016

Page 1

Editorial

Kenkyu Journal of Medical Science & Clinical Research

Open Access

Citation: Obulesu M (2016) Iron Chelation Therapy. KJ Medscicr 1: 100101

a free primary amino group available for the conjugation. These nanoparticles showed adsorption on lipoproteins such as low density lipoprotein (LDL). Since they mimic lipoproteins, they are first adsorbed on the low density lipoprotein receptors. Further they are uptaken by brain endothelial cells. Despite the better efficacy of the low molecular weight chelators and polymeric chelators, a few limitations impede their success. There has been an ambiguity whether polymeric chelators are mile stones in chelation therapy or a mirage.

4. Conclusion and Future Perspectives Although development of substantial iron chelators appears ambiguous, a few further studies may open a few novel avenues. In line with this, specific insights into conjugation of aminodiacetic acid ligands to biocompatible polymers such as poly (ethylene glycol) may significantly enhance systemic circulation, reduce toxicity and exhibit robust iron chelation.

Since

aminodiacetic acid containing compounds show better chelation efficacy, they can be used to develop potential armamentarium for iron overload diseases.

References: 1.

Philip E, Hallaway (1989) Proc Natl Acad. Sci. USA 86: 10108-10112.

2.

Obulesu (2016) Curr Drug Metab 17:142-149.

Copyright: © 2016 Obulesu M, This is an open-access article which is distributed under Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Volume 1, Issue 1 -KJMSCR-100101

www.kenkyuonline.org

Received: February 24, 2016; Accepted: February, 2016; Published: February, 2016

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