Iron carbohydrate nanoparticles are used to treat iron deficiency anemia in patients with chronic kidney disease. These nanomedicines are administered intravenously, and in the U.S. eight iron-carbohydrate drugs have been FDA approved. One product, sodium ferric gluconate, is available as both a brand (Ferrlecit) and a generic form. Sodium ferric gluconate is a complex colloidal nanoparticle composed of an iron-hydroxide core and a carbohydrate shell. Concern has been raised by the EMA (FDA equivalent in Europe) that generic iron colloid products can be toxic. It has been hypothesized that toxicity occurs because iron is released differently from the brand versus generic. The biological target of iron released from the nanoparticles is the protein transferrin, which delivers iron to cytoplasmic proteins for use or storage. Iron overload leads to saturated transferrin, and the remaining iron, termed labile iron, is transported into the cell where it can participate in chemistry with oxygen species leading to toxicity. We conducted a two-way crossover pharmacokinetic study that involved administering each drug to healthy volunteers to determine if there were differences in iron release between the brand and generic iron gluconate drug products. We developed a highly sensitive bioanalytical approach to measure iron speciation in the blood plasma that involved coupling size exclusion chromatography to inductively coupled plasma mass spectrometry (LC-ICP-MS). This strategy allowed us to measure all the iron species in the plasma - total iron (TI), transferrin bond iron (TBI), drug bound iron (DBI) and labile iron (LI) simultaneously. This is first time that quantification of iron nanoparticles directly in patient samples has been achieved and resulted in the FDA issuing a new draft guidance for the approval of iron nanoparticle drugs utilizing this approach. Our clinical trial data along with comparative physiochemical characterization of the two ferric gluconate drugs will be presented.

Iron nanoparticle drugs: Bioanalytical and clinical studies

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.