Artificial Oxygen Carriers (Hemoglobin-Vesicles) as a Transfusion Alternative and for Oxygen Therapeutics

The most abundant protein in blood is hemoglobin (Hb, 12-15 g/dL), because oxygen is the most crucial for life activity. Hb is compartmentalized in RBCs, and the intracellular Hb concentration is 35 g/dL. In spite of its abundance in blood, Hb becomes toxic once it is released from RBCs. Hemoglobin-vesicles (HbV) are artificial oxygen carriers that mimic the cellular structure of RBCs to replace the blood transfusion. One injection of HbV in place of a blood transfusion is estimated as equivalent to a massive dose, such as several hundred milliliters or a few liters of normal blood contents. The fluid must therefore contain a sufficient amount of Hb, the binding site of oxygen, to carry oxygen like blood. Encapsulation of Hb can shield toxicity of molecular Hbs. HbV is much smaller than RBC (250 vs. 8000 nm), but it recreates the functions of RBCs; (i) The oxygen-unloading of HbV is slower than that of a cell-free Hb solution; (ii) The colloid osmotic pressure is zero. For a massive dosage, HbV has to be co-injected with a plasma substitute such as albumin; (iii) HbV is finally captured by RFS, and then degraded and excreted promptly; (iv) Co-encapsulation of an allosteric effector regulates oxygen-affinity; (v) Hemolysis is minimal during circulation and the lipid bilayer membrane prevents a direct contact of Hb and vasculature; (vi) Hb encapsulation retards reaction of NO, and HbV does not induce vasoconstriction. The obvious advantages of HbV are that it is pathogen free and blood type antigen free; moreover, it can withstand long-term storage for stockpiling. HbV has a variety of potential applications not only as a transfusion alternative but also as an oxygen therapeutic fluid that cannot be attained by the present RBC transfusion.