A comprehensive study of intravenous iron-carbohydrate nanomedicines: From synthesis methodology to physicochemical and pharmaceutical characterization

Abstract

Administration of intravenous iron is pivotal in the management of iron-deficiency anemia patients. In the past, parenteral iron was administrated as a ferric hydroxide complex that caused severe toxic reactions. The introduction of compounds containing iron in a core surrounded by a carbohydrate shell has circumvented this problem. Intravenous iron complexes, such as iron sucrose and iron carboxymaltose, consist of a polynuclear Fe (III)-oxyhydroxide/oxide core that is coated with a specific carbohydrate molecule. The carbohydrate shell stabilizes the insoluble iron core particles in colloidal suspension form and slows down the release of iron. Moreover, the carbohydrate shell chemistry differences influence the stability of the complex and iron release rate. In particular, this paper discusses the preparation method, physicochemical properties, and characteristics of iron sucrose, ferric derisomaltose, iron carboxymaltose, and ferumoxytol. These products differ in their physicochemical and clinical properties such as molecular weight distribution, particle size, zeta potential, free, and labile iron content, stability and release of iron in serum, and maximum tolerated dose. The first-generation of intravenous iron formulations were replaced with new intravenous iron dextran–free formulations, due to an elevated risk of anaphylactic reactions. Comparatively, the third-generation intravenous iron formulations, such as ferric derisomaltose, iron carboxymaltose, and ferumoxytol, allow higher doses of iron due to high complex stability and safety than the second generation formulations like iron sucrose.