Using DLS, ELS and SAXS to Study Ferric Nanoparticles Stabilized Using Different Oligosaccharides

DLS and SAXS are highly complementary particle analysis techniques, delivering information not only on particle size but also on particle shape and core-shell structure. In addition, ELS provides data about colloidal stability by measuring the surface charge of particles. In the present application report we highlight the complementarity of these 3 techniques for the characterization of different iron-carbohydrate complexes used for intravenous iron therapy.

Introduction

Depending on age, health condition and weight, the human body naturally contains 2 to 4 grams of iron. The majority of the body’s iron is bound to hemoglobin, which creates a protein complex that is able to bind the oxygen in the red blood cells. Iron is also bound to other proteins such as hemosiderin, myoglobin, transferrin, and ferritin, in which iron is stored and released to the organism when needed. Iron deficiency is one of the most common nutritional deficiencies worldwide, and can be caused by:

  • Insufficient absorption, such as insufficient intake of food or malnutrition
  • Increased demand, in case of pregnancy, lactation or children and adolescents in growth
  • Increased loss, like acute or chronic blood loss or surgeries

Women of childbearing age, persons of advanced age, athletes and patients with chronic inflammatory diseases are at a particularly high risk of iron deficiency, and thus also to anemia. While milder cases can generally be treated by dietary changes or oral iron supplementation, more severe cases require intravenous iron therapy.
As iron cannot be injected directly into the bloodstream, intravenous iron preparations consist in iron carbohydrate complexes. These allow for the controlled release of iron in the bloodstream. The iron taken up by the cells is passed on to ferritin and transferrin, and is then used in the body.
Since high molecular weight iron infusions have often been associated with complications, low molecular weight preparations such as iron sucrose, ferric carboxymaltose or sodium ferric gluconate are now preferred. These preparations are colloidal dispersions with particles in the lower nanometer range. The particles are composed of an iron core stabilized by a carbohydrate shell.
In order to fulfill the strict requirements for pharmaceutical products, iron infusions have to be thoroughly and systematically characterized before reaching the market. In this application report, we analyze two different ferric nanoparticle formulations by means of their size, shape and zeta potential, using three techniques: DLS and ELS (dynamic and electrophoretic light scattering), and SAXS (small-angle X-ray scattering). We thus highlight the complementarity of these techniques for the full characterization of iron formulations (1).

References

1. Pal, Amy Barton. Complexity of intravenous iron nanoparticle formulations: implications for bioequivalence evaluation. Annals of the New York Academy of Sciences. 1-9, 2017

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