Battlefield mortality is a pressing problem, and internal bleeding causes the majority of these deaths. Uncontrollable internal bleeding is primarily in the torso of the body and cannot be easily constrained with devices such as tourniquets.  Based on the difficulty of access there is a need to develop a product that can target sites of injury to help facilitate the coagulation cascade, stopping the loss of blood, until surgical help can be administered. Nanoparticles are currently a highly explored field for drug delivery, and appear promising to help tackle the problem of uncontrollable internal bleeding. Polymers have desirable properties for nanoparticles targeted at drug delivery, such as biocompatibility and biodegradability. Polymers can also be used to adjust the charge that nanoparticles carry along with particle size. Polyphosphates are of interest as a coagulation accelerator based on their biocompatibility, half-life of 90 min (biodegradability) and they are known to be a potent hemostatic agent. Short chain polyphosphates (P60-P100) have been found to interact with multiple steps in the coagulation cascade, and have been shown to enhance coagulation. Functionalized targeting peptide sequences, also known as protease degradable cross-linkers, such as the KGGLVPRGSGK sequence, can be incorporated into the nanoparticle shell in varying concentrations to help locate the particles at the site of injury. This specific peptide sequence is cleaved by Thrombin, which will only be present at the wound site, anchoring the particles to this area for degradation. Thrombin will cleave the sequence, breaking down the polymer shell and release polyphosphate so it can participate in the coagulation cascade and control the bleeding. Non-protease degradable cross-linkers will also be explored to make control particles. Particles have been successfully synthesized in the size range of 50-250 nm.  This research has the potential to benefit not only the military but civilian trauma patients too.

Multifunctional nanoparticles for the targeted delivery of a coagulation amplifier to sites of internal hemorrhage

248th National Meeting (2014)

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