Iron sucrose and ferric carboxymaltose: no correlation between physicochemical stability and biological activity

Abstract

Intravenous iron preparations, like iron sucrose (IS) and ferric carboxymaltose (FCM) differ in their physicochemical stability. Thus differences in storage and utilization can be expected and were investigated in a non-clinical study in liver parenchyma HepG2-cells and THP-1 macrophages as models for toxicological and pharmacological target cells. HepG2-cells incorporated significant amounts of IS, elevated the labile iron pool (LIP) and ferritin and stimulated iron release. HepG2-cells had lower basal cellular iron and ferritin content than THP-1 macrophages, which showed only marginal accumulation of IS and FCM. However, FCM increased the LIP up to twofold and significantly elevated ferritin within 24 h in HepG2-cells. IS and FCM were non-toxic for HepG2-cells and THP-1 macrophages were more sensitive to FCM compared to IS at all concentrations tested. In a cell-free environment redox-active iron was higher with IS than FCM. Biostability testing via assessment of direct transfer to serum transferrin did not reflect the chemical stability of the complexes (i.e., FCM > IS). Effect of vitamin C on mobilisation to transferrin was an increase with IS and interestingly a decrease with FCM. In conclusion, FCM has low bioavailability for liver parenchyma cells, therefore liver iron deposition is unlikely. Ascorbic acid reduces transferrin-chelatable iron from ferric carboxymaltose, thus effects on hepcidin expression should be investigated in clinical studies.

Endothelium Response to Iron Sucrose Nanoparticles in Static Versus Dynamic Culture Model

“…3f, HUVECs ability to uptake Neural red dye was signi cantly decreased under static culture, con rming reduced cell viability, which is in agreement with other publications using conventional static culture. [15], [23] In this study, the investigation into cellular viability was performed using iron sucrose concentration in accordance with the clinical applied doses, subsequently our viability test re ects the potential misleading results obtained from conventional in vitro systems in comparison to an advanced dynamic culture model to mimic endothelium under physiological shear stress. There are a noticeable number of animal and clinical studies demonstrating the safety and effectiveness of intravenous iron sucrose for the treatment of iron de ciency.…”

Novel p53-dependent anticancer strategy by targeting iron signaling and BNIP3L-induced mitophagy

“…Following loading the cells with calcein-AM (0.25 μM) in 20 mM Hepes buffered serum-free growth medium for 15 minutes at 37°C and washings, they were incubated with medium with anti-calcein antibody and 20 mM Hepes. Anti-calcein antibody was prepared according to a protocol of William Breuer (Hebrew University of Jerusalem, Israel) as described by [ 54 ]. The anti-calcein antibody was used to quench fluorescence of extracellular calcein.…”