Poly(2-ethyl-2-oxazoline)-Conjugated Hemoglobins as a Red Blood Cell Substitute
Wataru Okamoto, Yuuki Hiwatashi, Tatsuhiro Kobayashi, Yoshitsugu Morita, Hiroto Onozawa, Masayuki Iwazaki, Mitsutomo Kohno, Hirotaka Tomiyasu, Ryota Tochinai, Radostina Georgieva, Hans Bäumler, Teruyuki Komatsu
Abstract
Hemoglobin wrapped covalently with poly(2-ethyl-2-oxazoline)s (POx-Hb) is characterized physicochemically and physiologically as an artificial O 2 carrier for use as a red blood cell (RBC) substitute. The POx-Hb is generated by linkage of porcine Hb surface-lysines to a sulfhydryl terminus of the POx derivative, with the average binding number of the polymers ascertained as 6. The POx-Hb shows moderately higher colloid osmotic activity and O 2 affinity than the naked Hb. Human adult HbA conjugated with POx also possesses equivalent features and O 2 binding properties. The POx-Hb solution exhibits good hemocompatibility, with no influence on the functions of platelets, granulocytes, and monocytes. Its circulation half-life in rats is 14 times longer than that of naked Hb. Hemorrhagic shock in rats is relieved sufficiently by infusion of the POx-Hb solution, as revealed by improvements of circulatory parameters. Serum biochemistry tests and histopathological observations indicate no acute toxicity or abnormality in the related organs. All results indicate that POx-Hb represents an attractive alternative for RBCs and a useful O 2 therapeutic reagent in transfusion medicine.