Liposome-Encapsulated Hemoglobin: Oxygen Binding Properties and Respiratory Function

Abstract

Lipid bilayer membranes have been used to encapsulate hemoglobin and organic phosphates, resulting in a synthetic red cell with oxygen-binding properties very similar to red blood cells (RBCs). In addition to the oxygen-binding parameters, we report here an improvement in the lipid formulation that confers upon the liposome-encapsulated hemoglobin (LEH) a circulation retention half-time of 15 to 20 hours in mice. Cooperative oxygen binding of the encapsulated hemoglobin is retained and the oxygen-binding affinity can be maintained at or below the level of fresh whole blood for many weeks by co-encapsulation of an appropriate concentration of pyridoxal-5-phosphate. A comparison of the kinetics of oxygen exchange across the membranes of the synthetic red cells and RBCs indicates that the increased surface to volume ratio of the much smaller synthetic red cells, coupled with their somewhat lower concentration of hemoglobin, results in more rapid rates of oxygen uptake and release than are seen with RBCs. Efficacy studies have begun and we report here the successful transfusion of rats with LEH. After greater than 90% exchange, LEH transfused rats were able to maintain activity with normal respiratory and cardiac function parameters.