Development of a Synthetic Blood Substitute Utilizing Hemoglobin Vesicles

The overall goal of our study was to further the development of a safe and effective oxygen-carrying red blood cell (RBC) substitute based on functional hemoglobin encapsulated within lipid vesicles (liposomes). Our studies demonstrated that liposome-encapsulated hemoglobin (LEH) provided an effective means of oxygen delivery in experimental animals. Our results indicated that exposure of experimental animal to liposomes made from conventional lipids was associated with significant immunotoxicity, as measured by impaired host resistance to infectious challenge. Our results thus far suggested that liposomes constructed with Stealth lipids were less immunotoxic than were liposomes made with conventional lipids. Both LEH formulations depressed phagocytic function as measured by ingestion of latex beads. Circulation half-life following 50% isovolumic exchange-transfusion in rats with LEH was about 20 hrs; 97% exchange-transfusion demonstrated efficacy in life support Met-Hb generation accompanying LEH processing (below 10 deg C) and 1 month storage (-20 deg C) appeared to be small with only a 3% and less than a 10% increase for encapsulated over precursor, respectively Oxygen affinity and cooperativity and steady shear viscosity values for LEH suspensions (30% by volume) appeared to be near the normal values expected for whole blood. Incubation in plasma at 37 deg C resulted in only a sm all amount of Hb release from LEH; also shear had very little effect on causing Hb leakage from LEH.