Pharmacokinetic study of enclosed hemoglobin and outer lipid component after the administration of hemoglobin vesicles as an artificial oxygen carrier

Kazuaki Taguchi, Yukino Urata, Makoto Anraku, Toru Maruyama, Hiroshi Watanabe, Hiromi Sakai, Hirohisa Horinouchi, Koichi Kobayashi, Eishun Tsuchida, Toshiya Kai, Masaki Otagiri

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The hemoglobin vesicle (HbV) is an artificial oxygen carrier that encapsulates a concentrated Hb solution in lipid vesicles (liposomes). The pharmacokinetic properties of HbV were investigated in mice and rats. With use of HbV in which the internal Hb was labeled with 125I (125I-HbV) and cell-free 125I-Hb, it was found that encapsulation of Hb increased the half-life by 30 times, accompanied by decreased distribution in both the liver and kidney. The half-life of HbV was increased, and the uptake clearance for the liver and spleen were decreased with increasing doses of HbV. In an in vitro study, the specific uptake and degradation of HbV in RAW 264.7 cells were found, but this was not the case for parenchymal and endothelial cells. The pharmacokinetics of HbV components (internal Hb and liposomal lipid) were also investigated using 125I-HbV and 3H-HbV (liposomal cholesterol was radio-labeled with tritium-3). The time courses for the plasma concentration curves of 125I-HbV, 3H-HbV, and iron derived from HbV suggest that HbV maintain an intact structure in the blood circulation up to 24 h after injection. 125I-HbV and 3H-HbV were distributed mainly to the liver and spleen. Internal Hb disappeared from both the liver and spleen 5 days after injection, and the liposomal cholesterol disappeared at approximately 14 days. Internal Hb was excreted into the urine and cholesterol into feces via biliary excretion. These results suggest that the HbV has a reasonable blood retention and metabolic and excretion performance and could be used as an oxygen carrier.

Original languageEnglish
Pages (from-to)1456-1463
Number of pages8
JournalDrug Metabolism and Disposition
Volume37
Issue number7
DOIs
Publication statusPublished - 2009 Jul 1
Externally publishedYes

Fingerprint

Hemoglobins
Pharmacokinetics
Oxygen
Lipids
Spleen
Liver
Cholesterol
Half-Life
Injections
Tritium
Blood Circulation
Radio
Feces
Liposomes
Iron
Endothelial Cells
Urine

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Pharmacokinetic study of enclosed hemoglobin and outer lipid component after the administration of hemoglobin vesicles as an artificial oxygen carrier. / Taguchi, Kazuaki; Urata, Yukino; Anraku, Makoto; Maruyama, Toru; Watanabe, Hiroshi; Sakai, Hiromi; Horinouchi, Hirohisa; Kobayashi, Koichi; Tsuchida, Eishun; Kai, Toshiya; Otagiri, Masaki.

In: Drug Metabolism and Disposition, Vol. 37, No. 7, 01.07.2009, p. 1456-1463.

Research output: Contribution to journalArticle

Taguchi, K, Urata, Y, Anraku, M, Maruyama, T, Watanabe, H, Sakai, H, Horinouchi, H, Kobayashi, K, Tsuchida, E, Kai, T & Otagiri, M 2009, 'Pharmacokinetic study of enclosed hemoglobin and outer lipid component after the administration of hemoglobin vesicles as an artificial oxygen carrier', Drug Metabolism and Disposition, vol. 37, no. 7, pp. 1456-1463. https://doi.org/10.1124/dmd.109.027094
Taguchi, Kazuaki ; Urata, Yukino ; Anraku, Makoto ; Maruyama, Toru ; Watanabe, Hiroshi ; Sakai, Hiromi ; Horinouchi, Hirohisa ; Kobayashi, Koichi ; Tsuchida, Eishun ; Kai, Toshiya ; Otagiri, Masaki. / Pharmacokinetic study of enclosed hemoglobin and outer lipid component after the administration of hemoglobin vesicles as an artificial oxygen carrier. In: Drug Metabolism and Disposition. 2009 ; Vol. 37, No. 7. pp. 1456-1463.
@article{679e38d33d254a53b280122e1397125e,
title = "Pharmacokinetic study of enclosed hemoglobin and outer lipid component after the administration of hemoglobin vesicles as an artificial oxygen carrier",
abstract = "The hemoglobin vesicle (HbV) is an artificial oxygen carrier that encapsulates a concentrated Hb solution in lipid vesicles (liposomes). The pharmacokinetic properties of HbV were investigated in mice and rats. With use of HbV in which the internal Hb was labeled with 125I (125I-HbV) and cell-free 125I-Hb, it was found that encapsulation of Hb increased the half-life by 30 times, accompanied by decreased distribution in both the liver and kidney. The half-life of HbV was increased, and the uptake clearance for the liver and spleen were decreased with increasing doses of HbV. In an in vitro study, the specific uptake and degradation of HbV in RAW 264.7 cells were found, but this was not the case for parenchymal and endothelial cells. The pharmacokinetics of HbV components (internal Hb and liposomal lipid) were also investigated using 125I-HbV and 3H-HbV (liposomal cholesterol was radio-labeled with tritium-3). The time courses for the plasma concentration curves of 125I-HbV, 3H-HbV, and iron derived from HbV suggest that HbV maintain an intact structure in the blood circulation up to 24 h after injection. 125I-HbV and 3H-HbV were distributed mainly to the liver and spleen. Internal Hb disappeared from both the liver and spleen 5 days after injection, and the liposomal cholesterol disappeared at approximately 14 days. Internal Hb was excreted into the urine and cholesterol into feces via biliary excretion. These results suggest that the HbV has a reasonable blood retention and metabolic and excretion performance and could be used as an oxygen carrier.",
author = "Kazuaki Taguchi and Yukino Urata and Makoto Anraku and Toru Maruyama and Hiroshi Watanabe and Hiromi Sakai and Hirohisa Horinouchi and Koichi Kobayashi and Eishun Tsuchida and Toshiya Kai and Masaki Otagiri",
year = "2009",
month = "7",
day = "1",
doi = "10.1124/dmd.109.027094",
language = "English",
volume = "37",
pages = "1456--1463",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "7",

}

TY - JOUR

T1 - Pharmacokinetic study of enclosed hemoglobin and outer lipid component after the administration of hemoglobin vesicles as an artificial oxygen carrier

AU - Taguchi, Kazuaki

AU - Urata, Yukino

AU - Anraku, Makoto

AU - Maruyama, Toru

AU - Watanabe, Hiroshi

AU - Sakai, Hiromi

AU - Horinouchi, Hirohisa

AU - Kobayashi, Koichi

AU - Tsuchida, Eishun

AU - Kai, Toshiya

AU - Otagiri, Masaki

PY - 2009/7/1

Y1 - 2009/7/1

N2 - The hemoglobin vesicle (HbV) is an artificial oxygen carrier that encapsulates a concentrated Hb solution in lipid vesicles (liposomes). The pharmacokinetic properties of HbV were investigated in mice and rats. With use of HbV in which the internal Hb was labeled with 125I (125I-HbV) and cell-free 125I-Hb, it was found that encapsulation of Hb increased the half-life by 30 times, accompanied by decreased distribution in both the liver and kidney. The half-life of HbV was increased, and the uptake clearance for the liver and spleen were decreased with increasing doses of HbV. In an in vitro study, the specific uptake and degradation of HbV in RAW 264.7 cells were found, but this was not the case for parenchymal and endothelial cells. The pharmacokinetics of HbV components (internal Hb and liposomal lipid) were also investigated using 125I-HbV and 3H-HbV (liposomal cholesterol was radio-labeled with tritium-3). The time courses for the plasma concentration curves of 125I-HbV, 3H-HbV, and iron derived from HbV suggest that HbV maintain an intact structure in the blood circulation up to 24 h after injection. 125I-HbV and 3H-HbV were distributed mainly to the liver and spleen. Internal Hb disappeared from both the liver and spleen 5 days after injection, and the liposomal cholesterol disappeared at approximately 14 days. Internal Hb was excreted into the urine and cholesterol into feces via biliary excretion. These results suggest that the HbV has a reasonable blood retention and metabolic and excretion performance and could be used as an oxygen carrier.

AB - The hemoglobin vesicle (HbV) is an artificial oxygen carrier that encapsulates a concentrated Hb solution in lipid vesicles (liposomes). The pharmacokinetic properties of HbV were investigated in mice and rats. With use of HbV in which the internal Hb was labeled with 125I (125I-HbV) and cell-free 125I-Hb, it was found that encapsulation of Hb increased the half-life by 30 times, accompanied by decreased distribution in both the liver and kidney. The half-life of HbV was increased, and the uptake clearance for the liver and spleen were decreased with increasing doses of HbV. In an in vitro study, the specific uptake and degradation of HbV in RAW 264.7 cells were found, but this was not the case for parenchymal and endothelial cells. The pharmacokinetics of HbV components (internal Hb and liposomal lipid) were also investigated using 125I-HbV and 3H-HbV (liposomal cholesterol was radio-labeled with tritium-3). The time courses for the plasma concentration curves of 125I-HbV, 3H-HbV, and iron derived from HbV suggest that HbV maintain an intact structure in the blood circulation up to 24 h after injection. 125I-HbV and 3H-HbV were distributed mainly to the liver and spleen. Internal Hb disappeared from both the liver and spleen 5 days after injection, and the liposomal cholesterol disappeared at approximately 14 days. Internal Hb was excreted into the urine and cholesterol into feces via biliary excretion. These results suggest that the HbV has a reasonable blood retention and metabolic and excretion performance and could be used as an oxygen carrier.

UR - http://www.scopus.com/inward/record.url?scp=67649415048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649415048&partnerID=8YFLogxK

U2 - 10.1124/dmd.109.027094

DO - 10.1124/dmd.109.027094

M3 - Article

C2 - 19364827

AN - SCOPUS:67649415048

VL - 37

SP - 1456

EP - 1463

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

SN - 0090-9556

IS - 7

ER -