Long-term pharmaceutical stability of liposome-encapsulated methemoglobin as an antidote for cyanide poisoning

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

Research output: Contribution to journalArticlepeer-review

Abstract

Liposome-encapsulated methemoglobin (metHb@Lipo) has been developed as a novel antidote for cyanide poisoning. Antidotes for lethal acute poisoning should be capable of being easily stored as ready-to-use formulations without temperature restrictions. Here, we investigated the pharmaceutical stability of the metHb@Lipo suspension after one-year storage as a ready-to-use formulation at 4 °C, room temperature (23–28 °C) and 37 °C. The liposomal integrity of metHb@Lipo was observed after one year of storage at all storage temperatures with no physicochemical change or methemoglobin leakage outside the liposome. Furthermore, the encapsulated methemoglobin remained intact without aggregation, fragmentation, denaturation, or dissociation of heme. Fresh and stored metHb@Lipo were equivalent in their binding affinity against cyanide. Moreover, all one-year stored metHb@Lipo suspensions improved the mortality rates of lethal cyanide poisoning mice comparable to fresh metHb@Lipo suspension. Additionally, all stored metHb@Lipo suspensions preserved high biocompatibility, including blood compatibility and the lack of organ toxicity. In conclusion, the metHb@Lipo suspension was a pharmaceutically stable antidote for cyanide poisoning for at least one year without any temperature restrictions.

Original languageEnglish
Article number121260
JournalInternational Journal of Pharmaceutics
Volume610
DOIs
Publication statusPublished - 2021 Dec 15

Keywords

  • Antidote
  • Cyanide poisoning
  • Liposome
  • Methemoglobin
  • Stability
  • Storage

ASJC Scopus subject areas

  • Pharmaceutical Science

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