Prof. Erin B. Lavik, Chemical, Biochemical and Environmental Engineering, UMBC, Baltimore, Maryland (Host: Prof. Robert Thorne)

Engineering Hemostatic Nanoparticles to Stop Internal Bleeding

     Traumatic injury is the leading cause of death for both men and women between the ages of 5 and 44 worldwide, and blood loss is the primary cause of death at acute time points.  Immediate intervention is essential to minimize mortality and yet there is a scarcity of technologies to address internal bleeding.

     We have developed functionalized nanoparticles based on poly(lactic-co-gycolic acid) (PLGA), poly(ethylene glycol) (PEG), and the arginine-glycine-aspartic acid (RGD) peptide which binds the glycoprotein IIb/IIIa receptor.  The receptor is only exposed on activated platelets. Our particles leverage the specificity of biology and are designed to help form stable clots faster to halt bleeding after intravenous administration.

     We have tested these hemostatic nanoparticles in a range of injury models including the femoral artery model and liver injury models. We have also tested these particles in a blast injury model of polytrauma and a model of brain injury with hemorrhaging. In all cases, we saw a reduction in bleeding, and in the case of lethal injury models, we saw significant improvements in survival. In both the blast injury models we see that the administration of the hemostatic nanoparticles reduces bleeding and this, in turn, leads to better behavioral outcomes. This suggests that reducing bleeding may be a critical component of providing neuroprotection after injury.

     The functionalized nanoparticles or hemostatic nanoparticles reduce bleeding in a number of models of trauma. Following administration, the particles participate in clot formation and can be found at the injury site post injury. The chemistry of the formulation including the length of the PEG arms and peptide play significant roles in the efficacy and clearance of the particles and provide means to tailor the particle behavior. This treatment has the potential to greatly impact survival outcomes related to internal hemorrhage and may lead to better functional outcomes more broadly.