A PEGylated bovine hemoglobin as a potent hemoglobin‐based oxygen carrier

Abstract

Hemoglobin (Hb)-based oxygen carriers (HBOCs) have been used as blood substitutes in surgery medicine and oxygen therapeutics for ischemic stroke. As a potent HBOC, the PEGylated Hb has received much attention for its oxygen delivery and plasma expanding ability. Two PEGylated Hbs, Euro-Hb, and MP4 have been developed for clinical trials, using human adult hemoglobin (HbA) as the original substrate. However, HbA was obtained from outdated human blood and its quantity available from this source may not be sufficient for mass production of PEGylated HbA. In contrast, bovine Hb (bHb) has no quantity constraints for its ample resource. Thus, bHb is of potential to function as an alternative substrate to obtain a PEGylated bHb (bHb-PEG). bHb-PEG was prepared under the same reaction condition as HbA-PEG, using maleimide chemistry. The structural, functional, solution and physiological properties of bHb-PEG were determined and compared with those of HbA-PEG. bHb-PEG showed higher hydrodynamic volume, colloidal osmotic pressure, viscosity and P than HbA-PEG. The high P of bHb can partially compensate the PEGylation-induced perturbation in the R to T state transition of HbA. bHb-PEG was non-vasoactive and could efficiently recover the mean arterial pressure of mice suffering from hemorrhagic shock. Thus, bHb-PEG is expected to function as a potent HBOC for its high oxygen delivery and strong plasma expanding ability. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:252-260, 2017.

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“…Upon successfully confirming the activity of the RBC-PFC formulation in vitro , an animal model of hemorrhagic shock was used to evaluate in vivo oxygen delivery efficacy. [44] To establish this model, mice were anesthetized, and a femoral artery was cannulated. Blood was then slowly withdrawn from the cannulated artery using a syringe pump such that the mean arterial pressure (MAP) reached a critical level of 35 mmHg.…”

Tumor-targeted hybrid protein oxygen carrier to simultaneously enhance hypoxia-dampened chemotherapy and photodynamic therapy at a single dose

“…Therefore, in the oxygen release experiment ( Figure 1 D ), ODC-HPOC more easily released its carried oxygen in deoxygenated PBS than free HbO 2 . Moreover, the high oxygen affinity may ensure the ODC-HPOCs retain oxygen before arriving at the hypoxic tumor region 44 .…”

In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion

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“…However, as the quantity of HbA available from donations may be insufficient for mass production of HBOCs, use of an alternative Hb, such as bovine hemoglobin (bHb), is necessary. Wang et al, showed that bHb-PEG is expected to function as a potent HBOC due to its high oxygen delivery and strong plasma-expanding ability [20].…”