Abstract
This study represents a new formulation of the novel Cyanide (CN) antidote, Dimethyl trisulfide (DMTS), for intramuscular administration. This is a naturally occurring organosulfur molecule with the capability of reacting with CN more efficiently than the present sulfur donor type CN therapy of Thiosulfate (TS). Two types of micelles (PEG2000-DSPE and PEG2000-DSPE/TPGS) were prepared and tested for their ability to encapsulate the liquid, highly lipophilic and volatile drug, DMTS. The micellar encapsulation for DMTS does not only eliminate the possible muscle necrosis at the injection sites, but the rate of evaporation within the micelles is suppressed, that can provide a level of stability for the formulation. The method of micelle preparation was optimized and it was demonstrated that the PEG2000-DSPE preparation can dissolve up to 2.0 mg/ml of the antidote candidate. Keeping the injection volume minimized this could provide a maximum DMTS dose of 12.5 mg/kg. However, even this low dose of DMTS showed a remarkable in vivo therapeutic efficacy (2 X LD50 protection) in a mice model when injected intramuscularly. These in vitro and in vivo findings proved the efficacy of DMTS in combating CN intoxication, and the presented work gives valuable insight to micelle preparation and sets the bases for a more advanced future formulation of DMTS.
Keywords: Cyanide antagonism, in vitro/in vivo efficacy, parenteral, PEG-PE micelles, solubility enhancement, sulfur donor.
Graphical Abstract
Related Books
Localized Micro/Nanocarriers for Programmed and On-Demand Controlled Drug Release
Mixed Polymeric Micelles for Osteosarcoma Therapy: Development and Characterization
A Comprehensive Text Book on Self-emulsifying Drug Delivery Systems
Nanomaterials: Evolution and Advancement towards Therapeutic Drug Delivery (Part II)
Nanomaterials: Evolution and Advancement Towards Therapeutic Drug Delivery (Part I)
27
2
1
1