Grant: Proof of Principle Program - Phase I

Halting severe bleeding is challenging. In some cases, a strong haemostatic agent can control severe external bleeding, but many times it cannot if bleeding originates inside a cavity, such as the nasal cavity or uterus. Haemostatic agents may clot blood that has already escaped from blood vessels, but to be effective, they must clot blood deep in the wound, at the site of damaged vessels. This is a challenge during epistaxis, surgery, childbirth, bleeds in people with haemophilia, and trauma resulting from situations such as automotive and hunting accidents or military combat. The best haemostatic agents used today only effectively initiate blood clotting millimeters or centimeters away from the damaged vessels because they cannot easily penetrate through blood flow. In order to transport coagulants deeper into wounds, we developed a new technology that foams and rapidly propels small particles through blood. It is composed of calcium carbonate, which is used in antacid tablets, and tranexamic acid, an agent used to stabilize blood clots. Each component of the agent is used clinically and is well-characterized in humans. Other therapeutic cargos, such as coagulation enzymes, are incorporated into the calcium carbonate microparticles and carried when they propel. No products like this have been used previously to treat bleeding or to deliver therapeutics into wounds. The proposed research will test the safety and efficacy of this technology using animal models. In preliminary data, the agent was highly effective in halting haemorrhage in two mouse models. In the proposed research we will test its effectiveness in a sheep model of intraoperative bleeding in the nasal cavity, and will determine if the material is safe using mice, rats and sheep. These tests are necessary to move the product toward planned clinical trials and commercialization.