title: Safety Evaluation of Hemoglobin-Albumin Cluster "HemoAct" as a Red Blood Cell Substitute.
abstract: A hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), a core-shell structured hemoglobin-albumin cluster designated as "HemoAct", is an O2-carrier designed for use as a red blood cell (RBC) substitute. This report describes the blood compatibility, hemodynamic response, and pharmacokinetic properties of HemoAct, and then explains its preclinical safety. Viscosity and blood cell counting measurements revealed that HemoAct has good compatibility with whole blood. Intravenous administration of HemoAct into anesthetized rats elicited no unfavorable increase in systemic blood pressure by vasoconstriction. The half-life of (125)I-labeled HemoAct in circulating blood is markedly longer than that of HSA. Serum biochemical tests conducted 7 days after HemoAct infusion yielded equivalent values to those observed in the control group with HSA. Histopathologic inspections of the vital organs revealed no marked abnormality in their tissues. All results indicate that HemoAct has sufficient preclinical safety as an alternative material for RBC transfusion.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Haruki
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Iwasaki
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Thoracic Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kamiyama
authors.affiliation: Department of Thoracic Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Mitsutomo
authors.initials: M
authors.lastname: Kohno
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Nagao
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Komatsu
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D019540:Area Under Curve; D001780:Blood Coagulation Tests; D001802:Blood Substitutes / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D017707:Erythrocyte Transfusion / Q000379:methods; D004912:Erythrocytes / Q000737:chemistry*; D006439:Hemodynamics; D006454:Hemoglobins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012709:Serum Albumin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution; D014783:Viscosity
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D012709:Serum Albumin