Liposome-Encapsulated Hemoglobin as an Effective Red Cell Surrogate: Biophysical, Bioengineering and Physiological Parameters.

Synthetic red cells based on the concept of liposome-encapsulated hemoglobin LEH are under investigation as a potential blood surrogate for on-site emergency use, with the principle Naval application being combat casualty care. In principle, hemoglobin solutions isolated from outdated whole blood are added to a homogeneous mixture of dry phospholipids lecithin and cholesterol, and the resulting two-phase dispersion is extruded under high pressure through narrow channels in a Microfluidizer. The resulting liposomes resemble miniature red blood cells without the blood group antigens, theoretically rendering them universally acceptable for transfusions. LEH has been shown to meet the physical and chemical criteria for an artificial oxygen transport system, and initial tests in rodents have been successful. The circulation half-life of LEH in mice is 15 to 20 hours. 90 exchange transfusion experiments have begun, and the LEH transfused rats are able to maintain normal cardiovascular parameters with red blood cell levels 50 below the lethal value for control animals. Large-scale efficacy and toxicity testing is required before clinical trials can be considered. With the completion of a feasibility study of various methods for producing LEH in quantity, we are now developing a sterile pilot plant. In addition to animal studies we will be preparing sterile LEH for use in collaborative studies of its effect on the clotting cascade, reticuloendothelial system RES function, isolated rat kidney metabolic maintenance and immune response.