Antidote against Cyanide Poisoning Developed from Artificial Red Blood Cells —Efficacy in the Treatment of Cyanide Poisoning with Both Fast-Acting and Versatile Antidote—
September 16, 2021
Keio University Faculty of Pharmacy
Nara Medical University
Sojo University DDS Research Institute
A research group at the Keio University Faculty of Pharmacy, Nara Medical University, and the Sojo University DDS Research Institute has developed liposome-encapsulated methemoglobin as an antidote against cyanide poisoning. These findings come from a research group led by Yuto Suzuki, a first-year doctorate student at the Keio University Graduate School of Pharmaceutical Sciences; Associate Professor Kazuaki Taguchi and Professor Kazuaki Matsumoto at the Keio University Faculty of Pharmacy; Professor Hiromi Sakai at Nara Medical University; and Specially Appointed Professor Masaki Otagiri at the Sojo University DDS Research Institute.
Cyanide can be found in everyday products such as metal-plated goods, insecticides, pesticides, and insulation (synthetic resin). At the same time, cyanide is highly poisonous and induces lethal poisoning when inhaled or ingested in large quantities. Cyanide poisoning occurs around the world under various circumstances, such as inhalation of cyanide-containing smoke created from burning buildings, accidental ingestion, and suicide. Nitrites are currently approved as cyanide poisoning antidotes. However, nitrites, which express a detoxification effect by converting hemoglobin in red blood cells to methemoglobin, have been unable to achieve rapid detoxification due to how long methemoglobin conversion takes. Furthermore, nitrites cannot be used to treat cyanide poisoning resulting from a fire (accompanied by carbon monoxide poisoning) due to the reduced oxygen-carrying capacity of red blood cells that have undergone methemoglobin conversion. For these reasons, it is paramount to improve the speed and versatility of cyanide poisoning treatment via nitrites.
In this project, researchers developed a novel cyanide poisoning antidote consisting of liposome-encapsulated methemoglobin (metHb@Lipo), which was obtained by oxidizing the hemoglobin contained within an artificial red blood cell preparation (Note 5). metHb@Lipo was designed with concept of artificially reproducing nitrites' antidotal mechanism that captures and detoxifies cyanide in the body by oxidizing hemoglobin into methemoglobin in red blood cells. In practice, metHb@Lipo bound with high affinity to cyanide, and increased survival among mouse models for lethal cyanide poisoning. Beyond extending the life of mouse models for lethal cyanide poisoning, metHb@Lipo was also more effective than nitrites in rapid detoxification and improving tissue hypoxia.
These outcomes demonstrated that metHb@Lipo is a more potent, rapid, and versatile antidote to cyanide poisoning than nitrites. The research team hypothesizes that this rapid detoxification was made possible because metHb@Lipo captures cyanide without needing to spend time converting hemoglobin into methemoglobin. They also believe that because metHb@Lipo does not convert hemoglobin to methemoglobin, the oxygen-carrying capacity of red blood cells is maintained, preventing hypoxia. Thus, metHb@Lipo can be used even when cyanide poisoning occurs in situations where nitrites are contraindicated (i.e. smoke inhalation from a fire), and its clinical use as a novel antidote to cyanide poisoning is expected to expand treatment options moving forward.
The results of this research were published in the September edition of the international journal on science and technology Journal of Controlled Release (digital edition published on July 15).
For further information, please refer to the following PDF file.