Preclinical In Vitro Safety Investigations of Submicron Sized Hemoglobin Based Oxygen Carrier HbMP-700.

Hemoglobin-based oxygen carriers (HBOCs) are being developed as oxygen and plasma volume-expanding therapeutics though their potential to promote oxidative tissue injury and nitric oxide (NO) scavenging combined with vasoconstriction has raised safety concerns. Therefore, we focused on these aspects during preclinical studies performed with the recently introduced hemoglobin microparticles (HbMP-700). Besides oxidative stress, we investigated possible vasoconstrictory influence of HBOCs as well as genetic toxicity. The novel developed HbMP-700 presented here provides a high oxygen affinity which prevents premature oxygen oversupply and avoids vasoconstriction of small blood vessels in vitro. The size of these particles is 700 nm (larger than 100 nm and smaller than 1000 nm) in order to prevent penetration through the blood vessel's endothelial gaps, NO-scavenging, and to avoid phagocytosis of large particles. We expect that the HbMP-700 meets the sophisticated requirements as a universal blood substitute.