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Abstract
Present studies have focused on nano-intercalated rhodanese in combination with sulfur donors to prevent cyanide lethality in a prophylactic mice model for future development of an effective cyanide antidotal system. Our approach is based on the idea of converting cyanide to the less toxic thiocyanate before it reaches the target organs by utilizing sulfurtransferases (e.g., rhodanese) and sulfur donors in a close proximity by injecting them directly into the blood stream. The inorganic thiosulfate (TS) and the garlic component diallydisulfide (DADS) were compared as sulfur donors with the nano-intercalated rhodanese in vitro and in vivo. The in vivo and in vitro experiments showed that DADS is not a more efficient sulfur donor than TS. However, the utilization of external rhodanese significantly enhanced the in vivo efficacy of both sulfur donor-nitrite combinations, indicating the potential usefulness of enzyme nano-delivery systems in developing antidotal therapeutic agents.
Acknowledgments
The authors are thankful to Dr Ray Yinn (ANP Technologies, Inc. 824 Interchange Boulevard, Newark, DE 19711) for providing the polyoxazoline-based dentritic polymers for these studies.
Declaration of interest: This study was supported by NIH: NIAID/USAMRICD Interagency Agreements (Y1-A1-6176-01/02 and A120-B.P2006/7-01), and the Army Medical Research Institute Of Chemical Defense (Dr Gary Rockwood) under the auspices of the U.S. Army Research Office Scientific Services Program administered by Battelle (Delivery Order 0878, Contract No. DAAD19-02-D-0001, TCN 06-170 and 08284), and the Robert A. Welch Foundation (x-0011) at Sam Houston State University, Huntsville TX. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.