Oxidized liposomal artificial red blood cells rescue azide-poisoned mice from lethal toxidrome by recovering cytochrome c oxidase activity

Yuto Suzuki, Kazuaki Taguchi, Satomi Hanyu, Tomoko Kure, Yuki Enoki, Masaki Otagiri, Hiromi Sakai, Kazuaki Matsumoto

Research output: Contribution to journalArticlepeer-review

Abstract

Exposure to azide compounds causes inhibition of cytochrome c oxidase in the mitochondria, leading to acute lethal poisoning. Although urgent pharmaceutical intervention is required for rescue from azide poisoning, no antidote exists worldwide. We hypothesized that methemoglobin (metHb) can be a promising material as an antidote for azide poisoning because metHb can strongly bind to azide. However, metHb administration is not feasible owing to in vivo instability and toxicity. We aimed to develop a feasible metHb-based antidote for azide poisoning, in which the inner hemoglobin of liposomal artificial red blood cells is oxidized by mixing with sodium nitrite. From the stopped-flow spectrophotometry analysis, as-prepared oxidized liposomal artificial red blood cells, which encapsulated metHb into the liposome (metHb@Lipo), the binding affinity of metHb@Lipo to azide was comparable to that of bare metHb. In addition, detoxification by metHb@Lipo increased the survival rate in lethal azide-poisoned model mice with recovery of cytochrome c oxidase activity, leading to the amelioration of acidosis and tissue oxidation. Furthermore, metHb@Lipo detoxification functioned even after 1 year of storage in a ready-to-use formulation. These results indicate that oxidized liposomal artificial red blood cells are a potent antidote for azide poisoning with favorable properties for use in critical care medicine.

Original languageEnglish
Article number103282
JournalJournal of Drug Delivery Science and Technology
Volume71
DOIs
Publication statusPublished - 2022 May

Keywords

  • Antidote
  • Azide poisoning
  • Detoxification
  • Liposome
  • Methemoglobin

ASJC Scopus subject areas

  • Pharmaceutical Science

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