The goal of this project is to develop a Root effect hemoglobin-based oxygen transport material for intravascular administration to enhance oxygen delivery to normal and malignant tissues. Root effect hemoglobins are found in the blood of some fish. The Root effect is an exaggerated Bohr effect wherein oxygen affinity is greatly decreased at acid pH. Root effect hemoglobins serve as pressure transducers. Because of the local variation in pH it is possible to load hemoglobin in the lungs at ambient oxygen pressure, i.e. a human breathing ambient air, and to deliver oxygen under vastly increased, even hyperbaric pressure, in acidic hypoxic tissues. A Root effect hemoglobin based oxygen transport material has the potential to enhance oxygen delivery to any acidic tissue: a decreased value of pH is commonly found in hypoxic normal and malignant tissues. The present work will address the specific problem of upscaling a procedure which has been established in the laboratory for encapsulation of exogenous Root effect hemoglobins into normal human red blood cells. This procedure has been successfully carried out in small batches sufficient to establish the efficacy of the product in rodent models. This Phase I project will attempt to develop procedures to upscale the encapsulation, a necessary hurdle which must be overcome before clinical trials can be undertaken.Proposed commercial application:This research is directed towards the development of a Root effect hemoglobin-based oxygen transport material which would have potential application in the treatment of a number of diseases including those resulting from normal tissue hypoxia such as myocardial infarction, cardiovascular accident, failure of tissue engraftment and wound healing, small vessel disease, etc. and to improve the oxygenation of malignant tumors to enhance the response to ionizing radiation and certain chemotherapeutic agents.National Institute of Heart, Lung, and Blood Institute (NHLBI)
