Siderophore‐Mimetic hydrogel for iron chelation therapy

Abstract

Two, three dihydroxybenzoic acid (DHBA), a portion of the metal chelating domain of enterobactin, was immobilized on crosslinked organic polymer polyallylamine (PAAm) and used as a chelating agent for iron removal from aqueous solutions. The swelling behavior of PAAm and PAAm hydrogels conjugated with dihydroxybenzoic acid and the effect of contact time on the swelling and binding capacity of the hydrogel was investigated at several pH values to define the absorption mechanism. Iron uptake kinetics followed the pseudosecond order Ho model and equilibrium was described by either Temkin or Freundlich isotherms. Maximum chelating capacities of the hydrogels were found to be 500-1500 mg Fe 3þ g À1 and 1500-2500 mg Fe 2þ g À1 forPAAm and PAAm/DHBA hydrogels, respectively, depending on the pH of the media. The selectivity of the conjugate hydrogel toward ferric ions was studied at several different pH values. At every pH ranging from 2 to 7.5, the conjugate hydrogel showed relatively high binding affinity for ferric ions. The selective and rapid, high affinity binding of iron by this siderophore-mimetic hydrogel offers potential application as a nonabsorbed chelator for iron in the gastrointestinal tract of patients suffering from iron overload diseases.

Biomimetic design of chelating interfaces

“…A representative compound of this group is desferrioxamine (DFO) [Figure (A)], which can interact with Fe 3+ to form an iron complex with an extremely high stability constant (log K = 30.6) . DFO has been approved by FDA as a drug and is widely used in medicine for clinical treatment of patients with iron overload …”

“…18 DFO has been approved by FDA as a drug and is widely used in medicine for clinical treatment of patients with iron overload. 22,23 The high specificity and affinity of the functional groups (e.g., HA) in siderophores for metal chelation has inspired researchers to design biomimetic metal chelating polymers [ Figure 1(B)]. The majority of published research in this area has focused on synthesis of free macromolecules, hydrogels, and resins with biomimetic metal chelating functionality.…”

Polymer antidotes for toxin sequestration

“…Moreover, intravenous administration of the deferoxamine conjugate does not produce severe hypotension as was observed when administering free-deferoxamine [110]. A siderophore mimic has also been evaluated by Mohammadi et al in the design of a non-absorbable hydrogel capable of chelating iron in the intestines [111]. In this strategy, primary amines of polyallylamine hydrogels were coupled to 2,3-dihydroxybenzoic acid.…”

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

“…It must be hydrophilic to allow swelling in aqueous media, providing accessibility of metal to the ligands as some metal chelating ligands are hydrophobic. Overall charge also matters, polycationic carriers (e.g., polyethyleneimine, polyallylamine and chitosan) [135,137,142,143] may Coulombically repulse metal cations, thus decreasing overall chelating capacity, while polyanionic (e.g., carboxymethyl cellulose and alginate) [100,143] may also nonspecifically bind other polyvalent cations, such as calcium or zinc.…”