FDA recently concurred that continued development of a multifunctional nano red blood cell (nRBC), polynitroxylated pegylated hemoglobin (PNPH), aka VitalHeme, for critical care and transfusion medicine was justified based on multiple pre-clinical animal efficacy studies and that nRBC can proceed to investigational new drug safety studies. This is a major breakthrough, especially after many failed attempts to develop such a therapeutic agent for un-met medical needs during the past half century. In the view of the FDA, nRBC clearly met the 2011 NIH/DOD/FDA Interagency Advisory Group's challenges to develop a next generation blood substitute that can not only perform as a bridge and/or alternative to blood transfusion but can also function as a therapeutic for the treatment of diseases where blood transfusion is not normally used.
nRBC is a multifuctional neuroprotective polynitroxylated pegylated hemoglobin (PNPH), aka VitalHemeTM, in the form of a ~7 nm nanoparticle. The 3D structure of nRBC is shown below as a dissected view with a core hemoglobin and its outer blue hydrated shell of 10 covalently attached polyethylene glycol molecules and an extra inner superoxide dismutase (SOD) mimetic shell (gold) formed by covalently attaching approximately 12 nitroxides with high spinning mobility (gold balls). The SOD mimetic shell prevents release of hemoglobin generated superoxide into the vascular space where it can cause vasoconstriction.
Below, RBCs with a diameter of 7,000 nm flowing through a blood vessel are shown.
A minute portion of above picture, magnified by ~10,000 fold, is shown below. A small section of a RBC is seen in the background and nRBCs are seen as they are freely flowing in the plasma phase where the nRBC, as a nano medicine, can extend its SOD mimetic activity to dismutate over production of plasma superoxide and thereby maintain or enhance vascular nitric oxide to deliver life-saving prevention and/or correction of inadequate blood flow and oxygen delivery in HS, TBI with HS, stroke, and sickle cell disease patients.