ABSTRACT
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References ........................................................................................................................... 217
There is an urgent need for a universally transfusable (nonallergenic), oxygen-carrying blood replacement fluid that can be used in emergency situations to provide temporary life support until a transfusion of whole blood can be administered. Numerous approaches have been taken in the attempt to develop materials that can deliver oxygen effectively and are safe for use as a red blood cell substitute; liposome-encapsulated Hb (LEH) has been developed more recently. 1·9 Liposome technology provides a mechanism for encapsulation and in vivo delivery of drugs, proteins, etc., which probably would otherwise be degraded, cleared rapidly, or toxic to the host. 10
The overall goal of our work is the development of a safe, efficacious, and commercially viable oxygen-carrying red blood cell substitute composed of hemoglobin solution encapsulated in a liposome. In these studies "Stealth®" liposomes (liposomes containing phosphatidylinositol, PI, or polyethyleneglycol distearoyl phosphatidylethanolamine, PEGPE) that are designed to evade recognition and rapid uptake by the reticuloendothelial system (more recently referred to as the mononuclear phagocytic system, MPS), 11·15 are used. Hemoglobin encapsulated in more conventionalliposomes have been shown to provide an effective means of oxygen delivery in vitro and in experimental animals.7· 16 However, it was recently found that phosphatidylglycerol (from egg) liposomes bound to rat platelets, which was mediated by complement. 17 Although LEH containing PI have also been shown to be efficacious,18 recent experiments19 suggest that such systems, by overloading the MPS,'0·c 1 cause alterations in phagocytic activity and increase host susceptibility to infectious challenge.c2 Our recent results with LEH containing PEG-PE suggest that they are less immunotoxic as they cause less adverse effects when treated animals were tested by infectious challenge. 19 It is the PEG-PE lipid component that is believed to be responsible for producing liposomes with surfaces that are sterically stabilized such that, e.g., plasma protein uptake is greatly reduced.23·36·38 This study encompasses the further development, characterization, and efficacy in life support of LEH using PEG-PE lipids.
