Biological responsiveness and metabolic performance of liposome-encapsulated hemoglobin (hemoglobin-vesicles) in apolipoprotein E-deficient mice after massive intravenous injection

Kazuaki Taguchi, Saori Nagao, Keishi Yamasaki, Hiromi Sakai, Hakaru Seo, Toru Maruyama, Masaki Otagiri

研究成果: Article査読

8 被引用数 (Scopus)

抄録

The hemoglobin-vesicle (HbV), a vesicle in which a concentrated human hemoglobin solution is encapsulated, was developed as an artificial oxygen carrier. Although HbV has a favorable safety, metabolic, and excretion performance in healthy animals, the effect of a massive amount of HbV, which also contains a large amount of a lipid component including cholesterol, on physiological response and metabolic performance under hyperlipidemic conditions is unclear. The aim of this study was to evaluate whether administration of HbV causes toxicity in apolipoprotein E-deficient mice (hyperlipidemic model mice). Apolipoprotein Edeficient mice were given a single injection of HbV (2000 mg hemoglobin/kg), and physiological responses and metabolic profiles were monitored for 14 d thereafter. All the mice tolerated the massive amount of HbV and survived, and adequate biocompatibility was observed. Serum biochemical parameters indicate that liver and kidney function were not remarkably affected, and morphological changes in the liver and spleen were negligible. Lipid parameters in serum were significantly increased until 3 d after HbV administration, but recovered within 7 d after the administration. In a pharmacokinetic study, HbV was mainly found distributed in the liver and spleen, and disappeared from the body within 14 d. In conclusion, even under conditions of hyperlipidemia, a massive dose of HbV and its components resulted in favorable biological compatibility, metabolic, and excretion profiles. These findings provide further support for the safety of HbV for clinical use.

本文言語English
ページ(範囲)1606-1616
ページ数11
ジャーナルBiological and Pharmaceutical Bulletin
38
10
DOI
出版ステータスPublished - 2015 10 1
外部発表はい

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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