Hemoglobin vesicles, polyethylene glycol (PEG)ylated liposomes developed as a red blood cell substitute, do not induce the accelerated blood clearance phenomenon in mice

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

研究成果: Article

29 引用 (Scopus)

抄録

The hemoglobin vesicle (HbV) is an artificial oxygen carrier encapsulating a concentrated hemoglobin solution in a liposome of which the surface is covered with polyethylene glycol (PEG). It was recently reported that repeated injections of PEGylated liposomes induce the accelerated blood clearance (ABC) phenomenon, in which serum anti-PEG IgM plays an essential role. To examine this issue, we investigated whether HbV induces the ABC phenomenon in mice at a dose of 0.1 mg Hb/kg, a dose that is generally known to induce the ABC phenomenon, or at 1400 mg Hb/kg, which is proposed for clinical use. At 7 days after the first injection of nonlabeled HbV (0.1 mg Hb/kg), the mice received HbV in which the Hb had been labeled with 125I. After a second injection, HbV was rapidly cleared from the circulation, and uptake clearances in liver and spleen were significantly increased. In contrast, at a dose of 1400 mg Hb/kg, the pharmacokinetics of HbV was negligibly affected by repeated injection. It is interesting to note that IgM against HbV was produced 7 days postinjection at both of the above doses, and their recognition site was determined to be 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine-N-PEG in HbV. These results suggest that a clinical dose of HbV does not induce the ABC phenomenon, and that suppression of ABC phenomenon is caused by the saturation of phagocytic processing by the mononuclear phagocyte system. Thus, we conclude that induction of the ABC phenomenon would not be an issue in the dose regimen used in clinical settings.

元の言語English
ページ(範囲)2197-2203
ページ数7
ジャーナルDrug Metabolism and Disposition
37
発行部数11
DOI
出版物ステータスPublished - 2009 11 1
外部発表Yes

Fingerprint

Blood Substitutes
Liposomes
Hemoglobins
Erythrocytes
Injections
Immunoglobulin M
Mononuclear Phagocyte System
Spleen
Pharmacokinetics
Oxygen

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

これを引用

Hemoglobin vesicles, polyethylene glycol (PEG)ylated liposomes developed as a red blood cell substitute, do not induce the accelerated blood clearance phenomenon in mice. / Taguchi, Kazuaki; Urata, Yukino; Anraku, Makoto; Watanabe, Hiroshi; Kadowaki, Daisuke; Sakai, Hiromi; Horinouchi, Hirohisa; Kobayashi, Koichi; Tsuchida, Eishun; Maruyama, Toru; Otagiri, Masaki.

:: Drug Metabolism and Disposition, 巻 37, 番号 11, 01.11.2009, p. 2197-2203.

研究成果: Article

Taguchi, K, Urata, Y, Anraku, M, Watanabe, H, Kadowaki, D, Sakai, H, Horinouchi, H, Kobayashi, K, Tsuchida, E, Maruyama, T & Otagiri, M 2009, 'Hemoglobin vesicles, polyethylene glycol (PEG)ylated liposomes developed as a red blood cell substitute, do not induce the accelerated blood clearance phenomenon in mice', Drug Metabolism and Disposition, 巻. 37, 番号 11, pp. 2197-2203. https://doi.org/10.1124/dmd.109.028852
Taguchi, Kazuaki ; Urata, Yukino ; Anraku, Makoto ; Watanabe, Hiroshi ; Kadowaki, Daisuke ; Sakai, Hiromi ; Horinouchi, Hirohisa ; Kobayashi, Koichi ; Tsuchida, Eishun ; Maruyama, Toru ; Otagiri, Masaki. / Hemoglobin vesicles, polyethylene glycol (PEG)ylated liposomes developed as a red blood cell substitute, do not induce the accelerated blood clearance phenomenon in mice. :: Drug Metabolism and Disposition. 2009 ; 巻 37, 番号 11. pp. 2197-2203.
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AU - Urata, Yukino

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AU - Watanabe, Hiroshi

AU - Kadowaki, Daisuke

AU - Sakai, Hiromi

AU - Horinouchi, Hirohisa

AU - Kobayashi, Koichi

AU - Tsuchida, Eishun

AU - Maruyama, Toru

AU - Otagiri, Masaki

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