September 3, 2021
Keio University Faculty of Pharmacy
Nara Medical University
DDS Research Institute, Sojo University
A research group from the Keio University Faculty of Pharmacy, Nara Medical University, and the DDS Research Institute, Sojo University has developed a liposome-based cyanide antidote in which methemoglobin is encapsulated by a lipid membrane. This research is the result of a group led by Yuto Suzuki, a first-year student in the Doctoral Programs at the Keio University Graduate School of Pharmaceutical Sciences; Associate Professor Kazuaki Taguchi and Professor Kazuaki Matsumoto of the same Faculty of Pharmacy; Professor Hiromi Sakai of Nara Medical University; and Project Professor Masaki Otagiri of the DDS Research Institute, Sojo University.
Cyanide compounds are found in everyday products such as metal plating supplies, insecticides, pesticides, and insulation materials (synthetic resins). However, cyanide compounds are highly toxic, causing lethal poisoning symptoms when inhaled or ingested in large quantities. Cyanide poisoning occurs in various situations both in Japan and abroad, including accidents such as inhalation of cyanide gas-containing smoke from building fires, accidental ingestion, and suicides. Currently, nitrite compounds are approved as a cyanide antidote. However, these compounds, which exert their detoxifying effect by converting hemoglobin in red blood cells to methemoglobin, take time to become effective and thus do not provide a rapid antidote. Furthermore, because the oxygen-carrying capacity of red blood cells is reduced when hemoglobin is converted to methemoglobin, nitrite compounds cannot be used for cyanide poisoning that occurs in fires (accompanied by carbon monoxide poisoning). Therefore, improvements in the immediacy and versatility of cyanide poisoning detoxification using nitrite compounds are desired.
In this study, we created a novel cyanide antidote, methemoglobin vesicles (metHb@Lipo), by oxidizing the hemoglobin encapsulated in hemoglobin vesicles, an artificial red blood cell preparation, to methemoglobin. This metHb@Lipo was designed based on the concept of artificially reproducing the detoxification mechanism of nitrite compounds, which capture cyanide in the body and exert a detoxifying effect by oxidizing hemoglobin in red blood cells to methemoglobin. In practice, metHb@Lipo showed a high binding affinity for cyanide and increased the survival rate of a lethal cyanide poisoning mouse model. Furthermore, metHb@Lipo prolonged the survival of the lethal cyanide poisoning mouse model more effectively than nitrite compounds, while also providing a rapid detoxifying effect and improving tissue hypoxia.
These findings indicate that metHb@Lipo is a more potent, rapid, and versatile antidote for cyanide poisoning than nitrite compounds. This is likely because metHb@Lipo can detoxify rapidly by capturing cyanide without requiring time for the methemoglobinization of hemoglobin. Additionally, since metHb@Lipo does not convert hemoglobin in red blood cells, it is thought to maintain the oxygen-carrying capacity of red blood cells and suppress hypoxia. Therefore, metHb@Lipo can be used for cyanide poisoning that occurs in situations where the use of nitrite compounds is difficult, such as in fires, and is expected to be used clinically as a new cyanide antidote that expands the scope of cyanide poisoning treatment.
The results of this research will be published in the September 2021 issue of the international academic journal "Journal of Controlled Release" (the online version was published on July 15).
For the full press release, please see below.