Hemoglobin-Based Oxygen Carrier Microparticles: Synthesis, Properties, and In Vitro and In Vivo Investigations

被引:76
|
作者
Xiong, Yu [1 ]
Steffen, Axel [1 ]
Andreas, Kristin [4 ,5 ]
Mueller, Susanne [2 ,3 ]
Sternberg, Nadine [1 ]
Georgieva, Radostina [1 ]
Baeumler, Hans [1 ]
机构
[1] Charite, Inst Transfus Med, D-10117 Berlin, Germany
[2] Charite, Dept Expt Neurol, D-10117 Berlin, Germany
[3] Charite, Ctr Stroke Res Berlin, D-10117 Berlin, Germany
[4] Charite, Tissue Engn Lab, D-10117 Berlin, Germany
[5] Charite, Dept Rheumatol & Clin Immunol, Berlin Brandenburg Ctr Regenerat Therapies, D-10117 Berlin, Germany
关键词
BOVINE HEMOGLOBIN; BLOOD SUBSTITUTES; POLYMERIZED HEMOGLOBIN; PROTEIN ENCAPSULATION; MICROCAPSULES; TRIAL; METHEMOGLOBIN; MULTICENTER; PARTICLES; CAPSULES;
D O I
10.1021/bm301085x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bovine hemoglobin microparticles (Hb-MPs) as suitable oxygen carriers are fabricated easily by three key steps: coprecipitation of Hb and CaCO3 to make Hb-CaCO3-microparticles (Hb-CaCO3-MPs), cross-linking by glutaraldehyde (GA) to polymerize the Hb and dissolution of CaCO3 template to obtain pure Hb-MPs. The Hb entrapment efficiency ranged from 8 to 50% corresponding to a hemoglobin quantity per Hb-MP of at least one-third of that in one erythrocyte. The Hb-MPs are spherical, with an average diameter of 3.2 mu m and high oxygen affinity. The methemoglobin level was increased after preparation, but can be reduced to less than 7% with ascorbic acid. Phagocytosis assays showed low immunogenicity of Hb-MPs if the particles were cross-linked with low concentration of GA and treated with sodium borohydride. Magnetite-loaded Hb-MPs circulated up to 4 days after intravenous application.
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页码:3292 / 3300
页数:9
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