Abstract
Phosphate removal is both biologically and environmentally important. Biologically, hyperphosphatemia is a critical condition in end-stage chronic kidney disease patients. Patients with hyperphosphatemia are treated long-term with oral phosphate binders to prevent phosphate absorption to the body by capturing phosphate in the gastrointestinal (GI) tract followed by fecal excretion. Environmentally, phosphate levels in natural water resources must be regulated according to limits set forth by the US Environmental Protection Agency. By utilizing nanotechnology and ligand design, we developed a new material to overcome limitations of traditional sorbent materials such as low phosphate binding capacity, slow binding kinetics, and negative interference by other anions. A phosphate binder based on iron-ethylenediamine on nanoporous silica (Fe-EDA-SAMMS) has been optimized for substrates and Fe(III) deposition methods. The Fe-EDA-SAMMS material had a 4-fold increase in phosphate binding capacity and a broader operating pH window compared to other reports. The material had a faster phosphate binding rate and was significantly less affected by other anions than Sevelamer HCl, the gold standard oral phosphate binder, and AG® 1-X8, a commercially available anion exchanger. It had less cytotoxicity to Caco-2 cells than lanthanum carbonate, another prescribed oral phosphate binder. The Fe-EDA-SAMMS also had high capacity for arsenate and chromate, two of the most toxic anions in natural water.
Highlights
Hyperphosphatemia is common in end-stage chronic kidney disease and dialysis patients totaling in 2 million worldwide [1]
The phosphate capture did not improve under the simulated gastric fluid (SGF) and SIF test matrices
Not a main focus of this paper, we have found Fe-EDASAMMS to be very efficacious at capturing arsenate and chromate, the two most hazardous oxometallate anions found in environmental water bodies [52]
Summary
Hyperphosphatemia is common in end-stage chronic kidney disease and dialysis patients totaling in 2 million worldwide [1]. The current prescribed phosphate binders in the market are calcium-based salts (acetate and carbonate), Sevelamer (hydrochloride and carbonate), lanthanum carbonate, aluminium salts and magnesium salts, which account for about $1 billion in global annual sales [2]. They have several drawbacks including high risk of hypercalcemia and calcification [3,4], high costs, low-to-moderate efficacy, adverse gastrointestinal effects, and high pill burden [5]. A new oral phosphate binder with high efficacy, low adverse effects, low cost, and low pill burden is needed. By ligand design of iron (Fe(III)) on ethylenediamine (EDA), we can achieve high phosphate binding efficacy that is less dependent on pHs and competing anions
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