Bacterial safety study of the production process of hemoglobin-based oxygen carriers

Submitting author affiliation:
Charité-Universitätsmedizin Berlin, Berlin, Germany

Beilstein Arch. 2021, 202181.

Published 23 Nov 2021

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Hemoglobin microparticles (HbMP) produced with a three-step procedure including co-precipitation of hemoglobin with manganese carbonate, protein crosslinking and dissolution of the carbonate template were shown to be suitable for application as artificial oxygen carriers. First preclinical safety investigations delivered promising results. Bacterial safety plays a decisive role during the production of the HbMP. Therefore, bioburden and endotoxin content of the starting materials (especially hemoglobin) and the final particle suspension are intensively tested. However, some bacteria may not have been detected by the standard tests due to low concentration. The aim of this study was to investigate how these bacteria would behave in the fabrication process. Biocidal effects are known for glutaraldehyde and for ethylenediaminetetraacetic acid, chemicals that are used in the fabrication process of HbMP. It could be shown that both chemicals prevent bacterial growth at the concentrations used during the HbMP fabrication. In addition, the particle production was carried out with hemoglobin solutions spiked with Escherichia coli or Staphylococcus epidermidis. No living bacteria could be detected in the final particle suspensions. Therefore, we conclude that the HbMP fabrication procedure is safe in respect of a bacterial contamination.

Keywords: hemoglobin; microparticles; bacterial safety; EDTA; glutaraldehyde

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Steffen, A.; Xiong, Y.; Georgieva, R.; Kalus, U.; Bäumler, H. Beilstein Arch. 2021, 202181. doi:10.3762/bxiv.2021.81.v1

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