Development of the liposome encapsulated stroma free hemoglobin (SFH) from out dated human red blood cells as the blood substitute.

We have developed and evaluated the liposome encapsulated high-concentrated (>45%) stroma free hemoglobin (SFH) : Neo Red Cell (NRC). SFH was encapsulated together with inositol-hexaphosphate (as an allosteric effector), coenzyme and substrates for reducing metHb back to oxyHb in liposomes. The NRC was subsequently coated with polyethylene glycol bound phosphatidylethanolamine as surface modifier to prevent aggregation of NRC in plasma. The oxygen affinity and the transport efficiency of NRC could be controlled as equal or more than those of the erythrocyte. The metHb formation was reduced 1%/hr to 0.3%/hr by the addition of metHb reduction system. The blood pressure increased transiently during injection, and then immediately returned to preinjection level. Our observations suggest that the NRC are efficient oxygen carriers without causing serious adverse reactions, with controllable metHb formation in vivo and during storage.