Tissue biodistribution of intravenous iron-carbohydrate nanomedicines differs between preparations with varying physicochemical characteristics in an anemic rat model

Intravenously administered iron-carbohydrate preparations are a structurally heterogenous class of nanomedicines. Iron biodistribution to target tissues is greatly affected by the physicochemical characteristics of these nanoparticles. Some regulatory agencies have recommended performing studies in animal models for biodistribution characterization and bioequivalence evaluation. In the present work, a systematic comparison of iron exposure, tissue biodistribution and pharmacodynamics of four intravenous iron-carbohydrates in anemic CD rats was conducted. A pilot study was performed to establish the anemic rat model, followed by a control study to evaluate the pharmacokinetics (serum iron, biodistribution) and pharmacodynamics (hematological parameters) in healthy and anemic controls and anemic rats receiving ferric carboxymaltose (FCM). The same parameters were then evaluated in a comparative study in anemic rats receiving FCM, iron sucrose (IS), iron isomaltoside 1000 (IIM), and iron dextran (ID). Despite similar serum iron profiles observed across the investigated nanomedicines, tissue iron biodistribution varied markedly between the individual intravenous iron-carbohydrate complexes. Tissue iron repletion differences were also confirmed by histopathology. These results suggest that employing serum iron profiles as a surrogate for tissue biodistribution may be erroneous. The variability observed in tissue biodistribution may indicate different pharmacodynamic profiles and warrants further study.