Polynitroxylated Hemoglobin as a Multifunctional Therapeutic for Critical Care and Transfusion Medicine

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Contribution to Book

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Selected Topics in Nanomedicine






Polynitroxylation (PN) technology is a chemical modification process, which covalently links multiple nitroxides to various macromolecules, including hemoglobin-based oxygen carriers (HBOCs). Like free nitroxides, PN products possess superoxide dismutase mimetic activity. In addition, when redox coupled with heme centers, polynitroxylated hemoglobins have catalase and peroxidase mimetic activities. PN of HBOCs allows the therapeutic benefits of nitroxides to be target delivered intravascularly. More significantly, it corrects the intrinsic toxicity of HBOCs and adds therapeutic neurovascular protective, anti-oxidant, and anti-inflammatory activities to these products. Results from multiple pre-clinical efficacy studies suggest that PN improves oxygen delivery by HBOCs through the correction of inadequate blood flow via prevention of both nitric oxide depletion and reperfusion/inflammation injuries after ischemia. PN of conjugated hemoglobins with hyper-colloid effects, such as polyethylene glycol or dextran conjugated hemoglobins, converts these HBOCs into small volume multifunctional hemodynamic therapeutics. Polynitroxylated pegylated hemoglobin (PNPH), in particular, has the potential to be a high-therapeutic-index next-generation HBOC for treatment of civilian un-met medical needs and military combat casualty care. Efficacy of PNPH has been demonstrated in models of traumatic brain injury with hemorrhagic shock, ischemic stroke, and sickle cell disease. This chapter traces the research leading to the development of PNPH.
Read More: http://www.worldscientific.com/doi/abs/10.1142/9789814472869_0008