Research Project
2868107
The goal of Phase I is to design a new class of hemoglobin molecules that work safely and effectively as oxygen carriers. The long-term goal is to optimize these solutions for blood replacement therapies based on efficacy of oxygen transport and expansion of blood volume. The chemistry must be cost-effective for commercialization. In Phase I, we describe a new chemistry for specific, controlled attachment of synthetic polyethylene glycol polymers (PEG) to the surface of the hemoglobin molecule. Critical physicochemical properties of hemoglobin solutions have been defined that work effectively at blood replacement. This is due primarily to the absence of a vasoconstrictive response to these solutions, a side-effect that is the rule rather than the exception in commercial hemoglobin-based oxygen carriers that are in clinical trials today. The key physicochemical properties are: I) high viscosity, 2) high colloid osmotic pressure, and 3) high oxygen affinity. The strategy to achieve this objective is already well- established . Phase I research will correlate number of PEG surface attachments versus length of PEG chains to optimize these properties. Phase II is designed to test these formulations in vitro for diffusive oxygen transport and in vivo for maintenance of tissue oxygenation. PROPOSED COMMERCIAL APPLICATIONS: The method to modify hemoglobin with polyethylene glycol has significant potential to be developed into a commercial product for use as a blood replacement. Such a product can be used in emergencies, war time, or any time blood is not available. Moreover, this product has the potential to be inexpensive and universally compatible with recipients.
