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Biophysical Analysis and Preclinical Pharmacokinetics-Pharmacodynamics of Tangential Flow Filtration Fractionated Polymerized Human Hemoglobin as a Red Blood Cell Substitute.
Greenfield, Alisyn; Lamb, Derek R; Gu, Xiangming; Thangaraju, Kiruphagaran; Setua, Saini; Yahya, Ahmad; Vahedi, Amid; Khan, Mohd Asim; Wang, Qihong; Buehler, Paul W; Palmer, Andre F.
Afiliación
  • Greenfield A; William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 452 CBEC, 151 West Woodruff Avenue, Columbus, Ohio 43210, United States.
  • Lamb DR; The Center for Blood Oxygen Transport and Hemostasis, Department of Pediatrics, The University of Maryland School of Medicine, Baltimore, Maryland 21201, United States.
  • Gu X; William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 452 CBEC, 151 West Woodruff Avenue, Columbus, Ohio 43210, United States.
  • Thangaraju K; The Center for Blood Oxygen Transport and Hemostasis, Department of Pediatrics, The University of Maryland School of Medicine, Baltimore, Maryland 21201, United States.
  • Setua S; The Center for Blood Oxygen Transport and Hemostasis, Department of Pediatrics, The University of Maryland School of Medicine, Baltimore, Maryland 21201, United States.
  • Yahya A; William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 452 CBEC, 151 West Woodruff Avenue, Columbus, Ohio 43210, United States.
  • Vahedi A; William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 452 CBEC, 151 West Woodruff Avenue, Columbus, Ohio 43210, United States.
  • Khan MA; William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, 452 CBEC, 151 West Woodruff Avenue, Columbus, Ohio 43210, United States.
  • Wang Q; The Center for Blood Oxygen Transport and Hemostasis, Department of Pediatrics, The University of Maryland School of Medicine, Baltimore, Maryland 21201, United States.
  • Buehler PW; The Center for Blood Oxygen Transport and Hemostasis, Department of Pediatrics, The University of Maryland School of Medicine, Baltimore, Maryland 21201, United States.
  • Palmer AF; Department of Pathology, The University of Maryland School of Medicine, Baltimore, Maryland 21201, United States.
Biomacromolecules ; 24(4): 1855-1870, 2023 04 10.
Article en En | MEDLINE | ID: mdl-36877888
Red blood cell (RBC) substitutes tested in late-phase clinical trials contained low-molecular-weight hemoglobin species (<500 kDa), resulting in vasoconstriction, hypertension, and oxidative tissue injury; therefore, contributing to poor clinical outcomes. This work aims to improve the safety profile of the RBC substitute, polymerized human hemoglobin (PolyhHb), via in vitro and in vivo screening of PolyhHb fractionated into four molecular weight brackets (50-300 kDa [PolyhHb-B1]; 100-500 kDa [PolyhHb-B2]; 500-750 kDa [PolyhHb-B3]; and 750 kDa to 0.2 µm [PolyhHb-B4]) using a two-stage tangential flow filtration purification process. Analysis showed that PolyhHb's oxygen affinity, and haptoglobin binding kinetics decreased with increasing bracket size. A 25% blood-for-PolyhHb exchange transfusion guinea pig model suggests that hypertension and tissue extravasation decreased with increasing bracket size. PolyhHb-B3 demonstrated extended circulatory pharmacokinetics, no renal tissue distribution, no aberrant blood pressure, or cardiac conduction effects, and may therefore be appropriate material for further evaluation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sustitutos Sanguíneos / Hemoglobinas Límite: Animals / Humans Idioma: En Revista: Biomacromolecules Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sustitutos Sanguíneos / Hemoglobinas Límite: Animals / Humans Idioma: En Revista: Biomacromolecules Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos