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A novel iron-conjugated acid-modified chitosan derivatives as an oral phosphate binding agent to improve phosphorus adsorption efficacy in vitro and in vivo, synthesis and their characterization

Lin, Wen Jen, Lee, Shu An
Carbohydrate polymers 2019 v.212 pp. 378-386
adsorption, appetite, binding agents, blood serum, cell viability, chitosan, citric acid, iron, oral administration, pH, patient compliance, patients, phosphates, phosphorus, rats, therapeutics
Current phosphate binders used for hyperphosphatemia treatment need large daily dose which make patients’ compliance worse and the therapeutic efficacy may not conform the expectation. In this study, three polyacid modified iron-based chitosan derivatives were developed as an oral phosphate binding agent to improve phosphorus adsorption efficacy. The result showed that modification of chitosan by citric acid (CA) could facilitate the conjugation of iron by two folds (272.0 ± 12.1–315.3 ± 20.5 mg Fe/g vs. 141.0 ± 4.9–156.5 ± 8.3 mg Fe/g). All of these iron-based acid-modified chitosan had acceptable safety with cell viability >75% in the concentration up to 250 μg/mL. The stability in terms of iron release in pH 1.0 for 2 h was in the order of DPCS-NAc-CA-Fe (8.9 ± 2.3%) < DPCS-CA-Fe (19.1 ± 4.1%) < DADPCS-CA-Fe (24.6 ± 2.6%) indicating DPCS-NAc-CA-Fe was the most stable one. These iron-based acid-modified chitosan derivatives efficiently adsorbed 255.7 ± 11.3–271.2 ± 19.3 mg of phosphate especially in simulated gastro pH 1.0 in vitro. Furthermore, oral administration of DPCS-NAc-CA-Fe significantly lowered serum phosphorus level from 5.82 ± 0.45 mg/dL to 4.84 ± 0.56 mg/dL (p < 0.01) at 0.25% low feeding dose for 3 weeks without losing of weight, appetite, and activity of Wistar rats.