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

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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.

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Acknowledgments

We are grateful to Prof. Bernhard Gmeiner who supplied us with human serum. Ms. Haider’s work for this paper was part of her master thesis at the University of Vienna, Austria, which was performed at the Medical University of Vienna, Austria. This work was supported by the Austrian Research Promotion Agency (FFG 832528).

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All the authors declared no competing interests.

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  1. Department of Medical Chemistry, Medical University of Vienna, Waehringerstr. 10, 1090, Vienna, Austria

    Monika Praschberger, Kathrin Haider, Carolin Cornelius, Markus Schitegg, Brigitte Sturm, Hans Goldenberg & Barbara Scheiber-Mojdehkar

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  1. Monika Praschberger
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  2. Kathrin Haider
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  3. Carolin Cornelius
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Correspondence to Barbara Scheiber-Mojdehkar.

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Praschberger, M., Haider, K., Cornelius, C. et al. Iron sucrose and ferric carboxymaltose: no correlation between physicochemical stability and biological activity. Biometals 28, 35–50 (2015). https://doi.org/10.1007/s10534-014-9801-0

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