The overall goal is to develop an oxygen-carrying red blood cell substitute to replace whole blood transfusions and/or an oxygen-carrying plasma expander to replace plasma and intravenous fluids used to treat trauma victims. By entrapping hemoglobin in long-circulating Stealth liposomes, which are designed to be less susceptible to phagocytosis by the reticuloendothelial system (RES) than ordinary liposomes, we hope to develop an oxygen carrying system that is substantially less immunotoxic than other experimental systems under development, such as ordinary liposomes. In the present program, we plan to investigate Stealth liposome entrapped hemoglobin in terms of its pharmacokinetics, systemic toxicity, cytotoxic effects and impairment/blockage of the RES. Stealth liposomes contain polyethylene glycol lipid derivatives which shield these lipid particles from RES recognition and uptake and significantly increase circulation time in the bloodstream. The long-term objective is the development of Stealth liposome hemoglobin formulations meeting pharmaceutical standards with respect to safety, efficacy, shelf-life and manufacturability.Awardee's statement of the potential commercial applications of the research:We hope to market a red blood cell substitute to replace whole blood transfusions, and an oxygen carrying plasma expander to replace plasma and intravenous fluids used to treat patients suffering from shock following traumatic injuries such as gunshot wounds, traffic accidents and surgery.National Heart, Lung and Blood Institute (NHLBI)
