Encapsulation of Hemoglobin in Liposomes

One strategy to deliver hemoglobin in an oxygen carrying fluid is based on the sequestration of hemoglobin in biocompatible carriers. Much of the current work in this field is focused on the use of liposomes. Liposomes are biodegradable capsules which permit the diffusion of oxygen while encapsulating hemoglobin within an aqueous environment. The encapsulation of hemoglobin in liposomes extends the circulation persistence and alters the biodistribution of free or chemically modified hemoglobin. Numerous animal studies have shown effective oxygen delivery by liposomes with hemoglobin in models of hypovolemia and hemorrhagic shock. The focus of much work to define consequences of encapsulated hemoglobin administration has been on the effects of large-dose liposome application. This work has been directed at discerning the effects of liposome-encapsulated hemoglobin on organs of the reticuloendothelial system, particularly the liver and spleen as these are the principal sites of liposome accumulation. A number of transient effects are observed following the administration of clinically relevant doses of liposome-encapsulated hemoglobin such as a rise in liver enzymes, thrombocytopenia, leukocytosis, and complement activation. More recent studies have examined differences in the vasoactivity of encapsulated vs. free hemoglobin. These studies indicate that encapsulation markedly attenuates the vasoactivity of hemoglobins in an isolated aortic ring model. Large-scale manufacturing methods to produce sterile filtered preparations have been developed which increase the opportunities for GMP production and commercial development. This review will touch upon these issues with reference to the historic and recent literature on the safety and efficacy of liposome-encapsulated hemoglobin.