title: Optimization of liposomal lipid composition for a new, reactive sulfur donor, and in vivo efficacy studies on mice to antagonize cyanide intoxication.
abstract: Present studies have focused on a novel cyanide antidotal system, on the coencapsulation of a new sulfur donor DTO with rhodanese within sterically stabilized liposomes. The optimal lipid composition for coencapsulation of DTO with rhodanese is the combination of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, cholesterol, cationic lipid (DOTAP), and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] ammonium salt (with molar ratios of 82.7 : 9.2 : 3.0 : 5.1). With the optimized compositions, prophylactic and therapeutic in vivo efficacy studies were carried out in a mice model. When DTO was coencapsulated with rhodanese and thiosulfate the prophylactic antidotal protection was 4.9 × LD(50). Maximum antidotal protection against cyanide intoxication (15 × LD(50)) was achieved with coencapsulated rhodanese and DTO/thiosulfate in combination with sodium nitrite. When applied therapeutically, 100% survival rate (6/6) was achieved at 20 mg/kg cyanide doses with the encapsulated DTO-rhodanese-thiosulfate antidotal systems with and without sodium nitrite. These data are indicating that the appropriately formulated DTO is a promising sulfur donor for cyanide antagonism.
authors.affiliation: Department of Chemistry, Sam Houston State University, Huntsville, TX 77341, USA.
authors.forename: Ilona
authors.initials: I
authors.lastname: Petrikovics
authors.forename: Prashanth
authors.initials: P
authors.lastname: Jayanna
authors.forename: Jonathan
authors.initials: J
authors.lastname: Childress
authors.forename: Marianna
authors.initials: M
authors.lastname: Budai
authors.forename: Sarah
authors.initials: S
authors.lastname: Martin
authors.forename: Galina
authors.initials: G
authors.lastname: Kuzmitcheva
authors.forename: Gary
authors.initials: G
authors.lastname: Rockwood