Home Medicine 6. IRON OXIDE NANOPARTICLE FORMULATIONS FOR SUPPLEMENTATION
Chapter
Licensed
Unlicensed Requires Authentication

6. IRON OXIDE NANOPARTICLE FORMULATIONS FOR SUPPLEMENTATION

  • Amy Barton Pai
Become an author with De Gruyter Brill
Explore this Subject How to publish with us
Essential Metals in Medicine: Therapeutic Use and Toxicity of Metal Ions in the Clinic
This chapter is in the book Essential Metals in Medicine: Therapeutic Use and Toxicity of Metal Ions in the Clinic

Abstract

Intravenous (IV) iron is widely used to provide supplementation when oral iron is ineffective or not tolerated. All commercially available intravenous iron formulations are comprised of iron oxyhydroxide cores coated with carbohydrates of varying structure and branch characteristics. The diameter of the iron-carbohydrate complexes ranges from 5-100 nm and meets criteria for nanoparticles. Clinical use of IV iron formulations entered clinical practice beginning of the late 1950s, which preceded the nanomedicine exploration frontier. Thus, these agents were approved without full exploration of labile iron release profiles or comprehensive biodistribution studies. The hypothesis for the pathogenesis of acute oxidative stress induced by intravenous iron formulations is the release of iron from the iron-carbohydrate structure, resulting in transient concentrations of labile plasma iron and induction of the Fenton chemistry and the Haber-Weiss reaction promoting formation of highly reactive free radicals such as the hydroxyl radical. Among available IV iron formulations, products with smaller carbohydrate shells are more labile and more likely to release labile iron directly into the plasma (i.e., before metabolism by the reticuloendothelial system). The proposed biologic targets of labile-iron-induced oxidative stress include nearly all systemic cellular components including endothelial cells, myocardium, liver as well as low density lipoprotein and other plasma proteins. Most studies have relied on plasma pharmacokinetic analyses that require many model assumptions to estimate contribution of the iron-carbohydrate complex to elevations in serum iron indices and hemoglobin. Additionally, the commercially available formulations have not been well studied with regard to optimal dosing regimens, long-term safety and comparative efficacy. The IV iron formulations fall into a class defined by the Food and Drug Administration as “Complex Drugs” and thus present considerable challenges for bioequivalence evaluation.

Abstract

Intravenous (IV) iron is widely used to provide supplementation when oral iron is ineffective or not tolerated. All commercially available intravenous iron formulations are comprised of iron oxyhydroxide cores coated with carbohydrates of varying structure and branch characteristics. The diameter of the iron-carbohydrate complexes ranges from 5-100 nm and meets criteria for nanoparticles. Clinical use of IV iron formulations entered clinical practice beginning of the late 1950s, which preceded the nanomedicine exploration frontier. Thus, these agents were approved without full exploration of labile iron release profiles or comprehensive biodistribution studies. The hypothesis for the pathogenesis of acute oxidative stress induced by intravenous iron formulations is the release of iron from the iron-carbohydrate structure, resulting in transient concentrations of labile plasma iron and induction of the Fenton chemistry and the Haber-Weiss reaction promoting formation of highly reactive free radicals such as the hydroxyl radical. Among available IV iron formulations, products with smaller carbohydrate shells are more labile and more likely to release labile iron directly into the plasma (i.e., before metabolism by the reticuloendothelial system). The proposed biologic targets of labile-iron-induced oxidative stress include nearly all systemic cellular components including endothelial cells, myocardium, liver as well as low density lipoprotein and other plasma proteins. Most studies have relied on plasma pharmacokinetic analyses that require many model assumptions to estimate contribution of the iron-carbohydrate complex to elevations in serum iron indices and hemoglobin. Additionally, the commercially available formulations have not been well studied with regard to optimal dosing regimens, long-term safety and comparative efficacy. The IV iron formulations fall into a class defined by the Food and Drug Administration as “Complex Drugs” and thus present considerable challenges for bioequivalence evaluation.

Chapters in this book

  1. Frontmatter i
  2. About the Editors v
  3. Historical Development and Perspectives of the Series vii
  4. Preface to Volume 19 ix
  5. Contents xiii
  6. Contributors to Volume 19 xix
  7. Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
  8. Contents of Volumes in the Metal Ions in Life Sciences Series xxv
  9. 1. METALS IN MEDICINE: THE THERAPEUTIC USE OF METAL IONS IN THE CLINIC 1
  10. 2. SMALL MOLECULES: THE PAST OR THE FUTURE IN DRUG INNOVATION? 17
  11. 3. IRON CHELATION FOR IRON OVERLOAD IN THALASSEMIA 49
  12. 4. IRONING OUT THE BRAIN 87
  13. 5. INFECTIONS ASSOCIATED WITH IRON ADMINISTRATION 123
  14. 6. IRON OXIDE NANOPARTICLE FORMULATIONS FOR SUPPLEMENTATION 157
  15. 7. BUILDING A TROJAN HORSE: SIDEROPHORE-DRUG CONJUGATES FOR THE TREATMENT OF INFECTIOUS DISEASES 181
  16. 8. DEVELOPING VANADIUM AS AN ANTIDIABETIC OR ANTICANCER DRUG: A CLINICAL AND HISTORICAL PERSPECTIVE 203
  17. 9. CHROMIUM SUPPLEMENTATION IN HUMAN HEALTH, METABOLIC SYNDROME, AND DIABETES 231
  18. 10. MANGANESE: ITS ROLE IN DISEASE AND HEALTH 253
  19. 11. COBALT-SCHIFF BASE COMPLEXES: PRECLINICAL RESEARCH AND POTENTIAL THERAPEUTIC USES 267
  20. 12. COPPER DEPLETION AS A THERAPEUTIC STRATEGY IN CANCER 303
  21. 13. METAL COMPOUNDS IN THE DEVELOPMENT OF ANTIPARASITIC AGENTS: RATIONAL DESIGN FROM BASIC CHEMISTRY TO THE CLINIC 331
  22. 14. CHEMICAL AND CLINICAL ASPECTS OF METAL-CONTAINING ANTIDOTES FOR POISONING BY CYANIDE 359
  23. SUBJECT INDEX 393
https://doi.org/10.1515/9783110527872-006

Chapters in this book

  1. Frontmatter i
  2. About the Editors v
  3. Historical Development and Perspectives of the Series vii
  4. Preface to Volume 19 ix
  5. Contents xiii
  6. Contributors to Volume 19 xix
  7. Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
  8. Contents of Volumes in the Metal Ions in Life Sciences Series xxv
  9. 1. METALS IN MEDICINE: THE THERAPEUTIC USE OF METAL IONS IN THE CLINIC 1
  10. 2. SMALL MOLECULES: THE PAST OR THE FUTURE IN DRUG INNOVATION? 17
  11. 3. IRON CHELATION FOR IRON OVERLOAD IN THALASSEMIA 49
  12. 4. IRONING OUT THE BRAIN 87
  13. 5. INFECTIONS ASSOCIATED WITH IRON ADMINISTRATION 123
  14. 6. IRON OXIDE NANOPARTICLE FORMULATIONS FOR SUPPLEMENTATION 157
  15. 7. BUILDING A TROJAN HORSE: SIDEROPHORE-DRUG CONJUGATES FOR THE TREATMENT OF INFECTIOUS DISEASES 181
  16. 8. DEVELOPING VANADIUM AS AN ANTIDIABETIC OR ANTICANCER DRUG: A CLINICAL AND HISTORICAL PERSPECTIVE 203
  17. 9. CHROMIUM SUPPLEMENTATION IN HUMAN HEALTH, METABOLIC SYNDROME, AND DIABETES 231
  18. 10. MANGANESE: ITS ROLE IN DISEASE AND HEALTH 253
  19. 11. COBALT-SCHIFF BASE COMPLEXES: PRECLINICAL RESEARCH AND POTENTIAL THERAPEUTIC USES 267
  20. 12. COPPER DEPLETION AS A THERAPEUTIC STRATEGY IN CANCER 303
  21. 13. METAL COMPOUNDS IN THE DEVELOPMENT OF ANTIPARASITIC AGENTS: RATIONAL DESIGN FROM BASIC CHEMISTRY TO THE CLINIC 331
  22. 14. CHEMICAL AND CLINICAL ASPECTS OF METAL-CONTAINING ANTIDOTES FOR POISONING BY CYANIDE 359
  23. SUBJECT INDEX 393
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2026 De Gruyter Brill
Downloaded on 24.1.2026 from https://www.degruyterbrill.com/document/doi/10.1515/9783110527872-006/html
Scroll to top button