Blood substitutes and uses thereof

The invention relates to blood substitute compositions, and methods of use thereof. Described herein are compositions in which hemoglobin is maintained substantially in the reduced form of hemoglobin as opposed to the oxidized methemoglobin form through inclusion of an oxido-reductase enzyme and reducing agent within a vesicle with the hemoglobin. The vesicles additionally can comprise a dismutase, a catalase, and an electron acceptor, each of which contribute to either the maintenance of hemoglobin in the active oxygen carrying state or provide a benefit not achieved with free hemoglobin.