Self-assembled Microparticles for Targeted Protein Delivery to Sites of Internal Hemorrhage

Uncontrolled hemorrhage is the leading cause of preventable death in the battlefield and is also the second leading cause of death in civilian trauma. A number of hemostatic agents have been successful in treating external hemorrhage, but an effective method for treating internal hemorrhage is yet to be found. Thrombin is an enzyme central to the coagulation cascade. The ability to safely deliver thrombin specifically to the sites of internal injury will prove to be an effective hemorrhage control. We are therefore interested in the development of biocompatible, synthetic microparticles that can be targeted to deliver thrombin to the site of injury where it can initiate rapid blood clotting. We have conducted a fundamental investigation into the development of spontaneously assembled, protein-encapsulating microparticles using poly-L-glutamate (PLE) with pentalysine, and the dependence of this phenomenon on solution pH, ionic strength, and polyelectrolyte concentration. Zeta-potential measurements were used to quantify changes in polyelectrolyte surface potential as a function of solution pH and ionic strength. This information was used to predict pH ranges and salt concentrations that will be conducive to PLE microparticles synthesis in solution with pentalysine via simple coacervation. These results will serve as a guide for the synthesis of microparticles for protein encapsulation and for the optimization of microparticle properties.