ArticleToxicology and environmental health sciences2025
Investigation of blood-brain barrier penetration and pharmacokinetics of a new formulation of cyanide antidote dimethyl trisulfide.
Article in Toxicology and environmental health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: During cyanide poisoning, the rescue of vital organs like the brain is urgent. However, due to the presence of the blood-brain barrier (BBB), the currently available cyanide antidotes cannot reach the brain. Dimethyl trisulfide (DMTS) is a potent cyanide antidote and has excellent BBB permeability. Nonetheless, its formulation and application are challenging due to its highly lipophilic profile. In this work, a novel DMTS formulation, called FF-DMTS, was investigated. Its effect on in vitro DMTS permeability through BBB models, cellular viability, and in vivo absorption were tested. Methods: The particle size was measured in FF-DMTS formulation. The permeability of DMTS in this new formulation was tested in BBB-PAMPA and in primary triple co-culture models of BBB. The effect of FF-DMTS on cellular viability was determined. To test the membrane and barrier integrity transendothelial electrical resistance (TEER) and cell layer impedance measurements, immunofluorescent stainings and the fluorescein permeability technique were applied. The pharmacokinetics of DMTS were revealed in blood and brain tissue. Results: The average size of micelles in FF-DMTS was 16 nm. The permeability of DMTS through BBB-PAMPA and cell culture model was 7.68 × 10 Conclusions: Here, we showed that the novel FF-DMTS formulation has good permeability through BBB and a remarkable pharmacokinetic profile. Therefore, further investigation of the efficacy of FF-DMTS for treating cyanide intoxication is important.
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