Liposome-encapsulated hemoglobin. History, preparation and evaluation

Liposome-encapsulated hemoglobin (LEH) can be considered the nearest to "artificial red cells" of any of the products currently under development. It consists of an artificial sphere, made up of phospholipids, which contains hemoglobin in some form in the center. Like other hemoglobin-based oxygen carrier (HBOCs), it is not a complete resuscitation fluid for shock. Intervention in severe hemorrhage requires more than the provision of enhanced oxygen-carrying capacity. Functional imaging using PET suggests that the oxygen carriers should also be able to deliver oxygen for its consumption in cellular metabolism. At the same time, pathophysiology related to hemorrhage calls for additional components in LEH formulation. Experience to date suggests that a complex LEH formulation containing inhibitors of complement activation and reperfusion injury, oncotic substance, long circulation, and functional T1/2, while being stable at wide range of temperatures and having minimal toxicity, needs further development. LEH continues to have great potential as part of an advanced oxygen-carrying resuscitative fluid. Furthermore, most of these properties can be adjusted by altering the properties of the lipid envelope. LEH preparations have been shown to transport oxygen in a variety of animal models. The reasons that LEH is not more advanced in preclinical and clinical development include inefficiency of production and very high costs. In addition, some formulations have activated the complement cascade, and others have been found to cause some of the problems of perfluorocarbon emulsions, which are also particulate in nature. Thus, control and stability of particle size are very important in minimizing toxic side effects.