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The Stability and Shelf-Life of Liposome Encapsulated Hemoglobin: A Potential Blood Substitute

Published online by Cambridge University Press:  26 February 2011

Alans Rudolph
Affiliation:
Biomolecular Engineering Branch, Code 6190, Naval Research Laboratory, Washington, DC 20375–5000
Lewis P. Stratton
Affiliation:
Biomolecular Engineering Branch, Code 6190, Naval Research Laboratory, Washington, DC 20375–5000
Wayne K. Knoll Jr.
Affiliation:
Geo-Centers Inc., 10903 Indian Head Highway, Fort Washington, MD 20744
Sandra Bayne
Affiliation:
Geo-Centers Inc., 10903 Indian Head Highway, Fort Washington, MD 20744
Frances Ligler
Affiliation:
Biomolecular Engineering Branch, Code 6190, Naval Research Laboratory, Washington, DC 20375–5000
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Abstract

For any viable blood substitute, questions of long-term storage and shelf-life must be addressed. Recently, we have made great progress in improving the stability of the blood substitute, liposome encapsulated hemoglobin (LEH). We have concentrated our efforts on protecting LEH in solution and in the long-term preservation of LEH by lyophilization. In particular, we have been able to retard and in some cases, reverse the oxidative process of metHb formation in solution by the addition of antioxidants such as NADH and glutathione. We have been able to regenerate Hb preparations with 60% metHb by the addition of 10 mM NADH and glutathione. In these preparations addition of these antioxidants results in a decrease of metHb levels from 62% to 15% over the course of 12.5 days at 4°C. We have also explored the use of protective solutes such as the disaccharide trehalose in the preservation of LEH in the freeze-dried state. Addition of increasing amounts of trehalose and other disaccharides results in the inhibition of lyophilization-induced fusion events and in the retention of hemoglobin within the unilamellar liposomal vesicles following rehydration.

Type
Research Article
Copyright
Copyright © Materials Research Society 1988

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