Structure of carbohydrate-bound polynuclear iron oxyhydroxide nanoparticles in parenteral formulations

Dina S. Kudasheva, Jriuan Lai, Abraham Ulman, Mary Cowman

Research output: Contribution to journalArticle

Abstract

Intravenous iron therapy is used to treat anemia associated with chronic kidney disease. The chemical structures of parenteral iron agents have not been characterized in detail, and correlations between structure, efficiency of iron delivery, and toxicity via catalysis of oxygen-derived free radical creation remain to be established. In this study, two formulations of parenteral iron have been characterized by absorption spectroscopy, X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), atomic force microscopy (AFM), and elemental analysis. The samples studied were Venofer® (Iron Sucrose Injection, USP) and Ferrlecit® (Sodium Ferric Gluconate in Sucrose Injection). The 250-800-nm absorption spectra and the XRD patterns showed that both formulations contain a mineral core composed of iron oxyhydroxide in the β-FeOOH mineral polymorph known as akaganeite. This was further confirmed for each formulation by imaging using TEM and AFM. The average core size for the nanoparticles, after dialysis to remove unbound or loosely bound carbohydrate, was approximately 3 ± 2 nm for the iron-sucrose, and approximately 2 ± 1 nm for the iron-gluconate. Each of the nanoparticles consists of a mineral core, surrounded by a layer of bound carbohydrate. The overall diameter of the average bead in the dialyzed preparations was approximately 7 ± 4 nm for the iron-sucrose, and 3 ± 1 nm for the iron-gluconate. Undialyzed preparations have particles with larger average sizes, depending on the extent of dilution of unbound and loosely bound carbohydrate. At a dilution corresponding to a final Fe concentration of 5 mg/mL, the average particle diameter in the iron-sucrose formulation was approximately 22 ± 9 nm, whereas that of the iron-gluconate formulation was approximately 12 ± 5 nm.

Original languageEnglish (US)
Pages (from-to)1757-1769
Number of pages13
JournalJournal of Inorganic Biochemistry
Volume98
Issue number11
DOIs
StatePublished - Nov 2004

Fingerprint

saccharated ferric oxide
Nanoparticles
Iron
Carbohydrates
Minerals
Atomic Force Microscopy
Transmission Electron Microscopy
X-Ray Diffraction
X ray diffraction analysis
Dilution
Atomic force microscopy
Transmission electron microscopy
Injections
Dialysis
ferric hydroxide
Polymorphism
Catalysis
Chronic Renal Insufficiency
Free Radicals
Toxicity

Keywords

  • AFM
  • Akaganeite
  • Iron oxyhydroxide
  • Iron-carbohydrate complex
  • Iron-sucrose injection
  • Parenteral formulations
  • Sodium ferric gluconate

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

Cite this

Structure of carbohydrate-bound polynuclear iron oxyhydroxide nanoparticles in parenteral formulations. / Kudasheva, Dina S.; Lai, Jriuan; Ulman, Abraham; Cowman, Mary.

In: Journal of Inorganic Biochemistry, Vol. 98, No. 11, 11.2004, p. 1757-1769.

Research output: Contribution to journalArticle

@article{bf57f87856cc449d9df60f5a5a611847,
title = "Structure of carbohydrate-bound polynuclear iron oxyhydroxide nanoparticles in parenteral formulations",
abstract = "Intravenous iron therapy is used to treat anemia associated with chronic kidney disease. The chemical structures of parenteral iron agents have not been characterized in detail, and correlations between structure, efficiency of iron delivery, and toxicity via catalysis of oxygen-derived free radical creation remain to be established. In this study, two formulations of parenteral iron have been characterized by absorption spectroscopy, X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), atomic force microscopy (AFM), and elemental analysis. The samples studied were Venofer{\circledR} (Iron Sucrose Injection, USP) and Ferrlecit{\circledR} (Sodium Ferric Gluconate in Sucrose Injection). The 250-800-nm absorption spectra and the XRD patterns showed that both formulations contain a mineral core composed of iron oxyhydroxide in the β-FeOOH mineral polymorph known as akaganeite. This was further confirmed for each formulation by imaging using TEM and AFM. The average core size for the nanoparticles, after dialysis to remove unbound or loosely bound carbohydrate, was approximately 3 ± 2 nm for the iron-sucrose, and approximately 2 ± 1 nm for the iron-gluconate. Each of the nanoparticles consists of a mineral core, surrounded by a layer of bound carbohydrate. The overall diameter of the average bead in the dialyzed preparations was approximately 7 ± 4 nm for the iron-sucrose, and 3 ± 1 nm for the iron-gluconate. Undialyzed preparations have particles with larger average sizes, depending on the extent of dilution of unbound and loosely bound carbohydrate. At a dilution corresponding to a final Fe concentration of 5 mg/mL, the average particle diameter in the iron-sucrose formulation was approximately 22 ± 9 nm, whereas that of the iron-gluconate formulation was approximately 12 ± 5 nm.",
keywords = "AFM, Akaganeite, Iron oxyhydroxide, Iron-carbohydrate complex, Iron-sucrose injection, Parenteral formulations, Sodium ferric gluconate",
author = "Kudasheva, {Dina S.} and Jriuan Lai and Abraham Ulman and Mary Cowman",
year = "2004",
month = "11",
doi = "10.1016/j.jinorgbio.2004.06.010",
language = "English (US)",
volume = "98",
pages = "1757--1769",
journal = "Journal of Inorganic Biochemistry",
issn = "0162-0134",
publisher = "Elsevier Inc.",
number = "11",

}

TY - JOUR

T1 - Structure of carbohydrate-bound polynuclear iron oxyhydroxide nanoparticles in parenteral formulations

AU - Kudasheva, Dina S.

AU - Lai, Jriuan

AU - Ulman, Abraham

AU - Cowman, Mary

PY - 2004/11

Y1 - 2004/11

N2 - Intravenous iron therapy is used to treat anemia associated with chronic kidney disease. The chemical structures of parenteral iron agents have not been characterized in detail, and correlations between structure, efficiency of iron delivery, and toxicity via catalysis of oxygen-derived free radical creation remain to be established. In this study, two formulations of parenteral iron have been characterized by absorption spectroscopy, X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), atomic force microscopy (AFM), and elemental analysis. The samples studied were Venofer® (Iron Sucrose Injection, USP) and Ferrlecit® (Sodium Ferric Gluconate in Sucrose Injection). The 250-800-nm absorption spectra and the XRD patterns showed that both formulations contain a mineral core composed of iron oxyhydroxide in the β-FeOOH mineral polymorph known as akaganeite. This was further confirmed for each formulation by imaging using TEM and AFM. The average core size for the nanoparticles, after dialysis to remove unbound or loosely bound carbohydrate, was approximately 3 ± 2 nm for the iron-sucrose, and approximately 2 ± 1 nm for the iron-gluconate. Each of the nanoparticles consists of a mineral core, surrounded by a layer of bound carbohydrate. The overall diameter of the average bead in the dialyzed preparations was approximately 7 ± 4 nm for the iron-sucrose, and 3 ± 1 nm for the iron-gluconate. Undialyzed preparations have particles with larger average sizes, depending on the extent of dilution of unbound and loosely bound carbohydrate. At a dilution corresponding to a final Fe concentration of 5 mg/mL, the average particle diameter in the iron-sucrose formulation was approximately 22 ± 9 nm, whereas that of the iron-gluconate formulation was approximately 12 ± 5 nm.

AB - Intravenous iron therapy is used to treat anemia associated with chronic kidney disease. The chemical structures of parenteral iron agents have not been characterized in detail, and correlations between structure, efficiency of iron delivery, and toxicity via catalysis of oxygen-derived free radical creation remain to be established. In this study, two formulations of parenteral iron have been characterized by absorption spectroscopy, X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), atomic force microscopy (AFM), and elemental analysis. The samples studied were Venofer® (Iron Sucrose Injection, USP) and Ferrlecit® (Sodium Ferric Gluconate in Sucrose Injection). The 250-800-nm absorption spectra and the XRD patterns showed that both formulations contain a mineral core composed of iron oxyhydroxide in the β-FeOOH mineral polymorph known as akaganeite. This was further confirmed for each formulation by imaging using TEM and AFM. The average core size for the nanoparticles, after dialysis to remove unbound or loosely bound carbohydrate, was approximately 3 ± 2 nm for the iron-sucrose, and approximately 2 ± 1 nm for the iron-gluconate. Each of the nanoparticles consists of a mineral core, surrounded by a layer of bound carbohydrate. The overall diameter of the average bead in the dialyzed preparations was approximately 7 ± 4 nm for the iron-sucrose, and 3 ± 1 nm for the iron-gluconate. Undialyzed preparations have particles with larger average sizes, depending on the extent of dilution of unbound and loosely bound carbohydrate. At a dilution corresponding to a final Fe concentration of 5 mg/mL, the average particle diameter in the iron-sucrose formulation was approximately 22 ± 9 nm, whereas that of the iron-gluconate formulation was approximately 12 ± 5 nm.

KW - AFM

KW - Akaganeite

KW - Iron oxyhydroxide

KW - Iron-carbohydrate complex

KW - Iron-sucrose injection

KW - Parenteral formulations

KW - Sodium ferric gluconate

UR - http://www.scopus.com/inward/record.url?scp=7644229289&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7644229289&partnerID=8YFLogxK

U2 - 10.1016/j.jinorgbio.2004.06.010

DO - 10.1016/j.jinorgbio.2004.06.010

M3 - Article

C2 - 15522403

AN - SCOPUS:7644229289

VL - 98

SP - 1757

EP - 1769

JO - Journal of Inorganic Biochemistry

JF - Journal of Inorganic Biochemistry

SN - 0162-0134

IS - 11

ER -