Safety Evaluation of Cellular-type Artificial Blood Based on Pharmacokinetic Analysis and Its Use in Medical Gas Delivery

Research output: Contribution to journalReview article

Abstract

Hemoglobin vesicles (HbVs) in which human hemoglobin is encapsulated in a phospholipid bilayer membrane (liposome) have been developed as artificial red blood cells. Although the effectiveness of HbVs, including their physicochemical characteristics and pharmacological effects, has been reported, data on the pharmacokinetic properties of HbVs are limited. Previously, we developed two kinds of radiolabeled HbV, 125I-HbV and 3H-HbV, in which the internal hemoglobin and lipid membranes were labeled with 125I and 3H, respectively. Using these isotope-labeled HbVs, we clarified the detailed pharmacokinetic properties of HbVs in healthy animals and experimental animal disease models of hemorrhagic shock, chronic cirrhosis, and hyperlipidemia. This review describes our previous results regarding the pharmacokinetic properties of HbVs, and we discuss the safety and usefulness of HbVs from the viewpoint of their pharmacokinetic characteristics. Furthermore, we have modified HbVs by employing them as a carbon monoxide (CO) carrier because the hemoglobin inside HbVs reversibly binds to CO, resulting in CO-bound HbVs (CO-HbVs). Here we report the potential of CO-HbVs for the treatment of intractable inflammatory disorders based on their therapeutic efficiency in experimental animal models.

Original languageEnglish
Pages (from-to)1381-1389
Number of pages9
JournalYakugaku zasshi : Journal of the Pharmaceutical Society of Japan
Volume138
Issue number11
DOIs
Publication statusPublished - 2018 Jan 1
Externally publishedYes

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Blood Substitutes
Hemoglobins
Pharmacokinetics
Gases
Safety
Carbon Monoxide
Animal Models
Animal Disease Models
Hemorrhagic Shock
Membrane Lipids
Hyperlipidemias
Liposomes
Isotopes

Keywords

  • artificial blood
  • carbon monoxide
  • drug delivery system
  • hemoglobin
  • liposome
  • pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

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abstract = "Hemoglobin vesicles (HbVs) in which human hemoglobin is encapsulated in a phospholipid bilayer membrane (liposome) have been developed as artificial red blood cells. Although the effectiveness of HbVs, including their physicochemical characteristics and pharmacological effects, has been reported, data on the pharmacokinetic properties of HbVs are limited. Previously, we developed two kinds of radiolabeled HbV, 125I-HbV and 3H-HbV, in which the internal hemoglobin and lipid membranes were labeled with 125I and 3H, respectively. Using these isotope-labeled HbVs, we clarified the detailed pharmacokinetic properties of HbVs in healthy animals and experimental animal disease models of hemorrhagic shock, chronic cirrhosis, and hyperlipidemia. This review describes our previous results regarding the pharmacokinetic properties of HbVs, and we discuss the safety and usefulness of HbVs from the viewpoint of their pharmacokinetic characteristics. Furthermore, we have modified HbVs by employing them as a carbon monoxide (CO) carrier because the hemoglobin inside HbVs reversibly binds to CO, resulting in CO-bound HbVs (CO-HbVs). Here we report the potential of CO-HbVs for the treatment of intractable inflammatory disorders based on their therapeutic efficiency in experimental animal models.",
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AB - Hemoglobin vesicles (HbVs) in which human hemoglobin is encapsulated in a phospholipid bilayer membrane (liposome) have been developed as artificial red blood cells. Although the effectiveness of HbVs, including their physicochemical characteristics and pharmacological effects, has been reported, data on the pharmacokinetic properties of HbVs are limited. Previously, we developed two kinds of radiolabeled HbV, 125I-HbV and 3H-HbV, in which the internal hemoglobin and lipid membranes were labeled with 125I and 3H, respectively. Using these isotope-labeled HbVs, we clarified the detailed pharmacokinetic properties of HbVs in healthy animals and experimental animal disease models of hemorrhagic shock, chronic cirrhosis, and hyperlipidemia. This review describes our previous results regarding the pharmacokinetic properties of HbVs, and we discuss the safety and usefulness of HbVs from the viewpoint of their pharmacokinetic characteristics. Furthermore, we have modified HbVs by employing them as a carbon monoxide (CO) carrier because the hemoglobin inside HbVs reversibly binds to CO, resulting in CO-bound HbVs (CO-HbVs). Here we report the potential of CO-HbVs for the treatment of intractable inflammatory disorders based on their therapeutic efficiency in experimental animal models.

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