Mechanistic Data to Support Iron-Carbohydrate Nanoparticle PBPK Models

Intravenous iron-carbohydrate complexes are nanomedicines that are widely used globally to treat iron deficiency and iron deficiency anemia associated with a wide spectrum of disease states. Despite being widely used in clinical practice for more than seven decades, the understanding of their in vivo disposition including tissue biodistribution and kinetics of the nanoparticle degradation at the cellular level, is not well understood. Moreover, the critical quality attributes that influence in vivo pharmacokinetics have not been fully defined. In particular, the particle size and the carbohydrate moiety appear to have an influential role in how the nanoparticulate iron-carbohydrate complex interacts with the biological system. Developing a physiologically based pharmacokinetic (PBPK) model would facilitate a deeper understating of the key nanomedicine attributes that predict in vivo performance. This program will describe new mechanistic data focused on iron nanoparticle cellular uptake and the relationship of physicochemical parameters to biodistribution in vivo.