title: Efficacy of a nanocochleate-encapsulated 3,5-diaryl-s-triazole derivative in a murine model of graft-versus-host disease.
abstract: We have previously demonstrated that the compound 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole exerts immunosuppressive effects in several experimental models of autoimmunity. These results were achieved by subcutaneously administering ST1959 after dissolution in an oily vehicle, because of its poor water solubility. To circumvent this problem, we sought to determine whether nanocochleate technology could be successfully exploited to deliver ST1959 and protect mice undergoing lethal acute graft-versus-host disease (GVHD). Orally-administered encochleated ST1959 significantly protected animals from lethality, resulting in survival rates of 57% and 100% at doses of 2 and 10 mg/kg, respectively, whereas oral administration of 2 mg/kg ST1959, mixed with empty nanocochleates, was completely inactive. Increased survival was associated with diminished serum chemokine levels and donor CD8+ T cells in the spleen of ST1959-treated mice. Moreover, ST1959 treatment significantly counteracted GVHD-induced normocitic anemia by increasing hemoglobin, hematocrit, platelet, and red and white blood cell counts. Overall, these data show that orally-administered encochleated ST1959 significantly protects mice from GVHD.
authors.affiliation: Sigma-Tau S.p.A Research and Development, Pomezia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Campo
authors.forename: Brunilde
authors.initials: B
authors.lastname: Arseni
authors.forename: Stefania
authors.initials: S
authors.lastname: Rossi
authors.forename: Valeria
authors.initials: V
authors.lastname: D'Alessio
authors.forename: Ruying
authors.initials: R
authors.lastname: Lu
authors.forename: Joel
authors.initials: J
authors.lastname: Ngoje
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Ahl
authors.forename: Susan
authors.initials: S
authors.lastname: Bonitz
authors.forename: Raphael
authors.initials: R
authors.lastname: Mannino
authors.forename: Diletta
authors.initials: D
authors.lastname: Di Mitri
authors.forename: Luca
authors.initials: L
authors.lastname: Battistini
authors.forename: Paolo
authors.initials: P
authors.lastname: Carminati
authors.forename: Rita
authors.initials: R
authors.lastname: De Santis
authors.forename: Vito
authors.initials: V
authors.lastname: Ruggiero
mesh_terms: D000284:Administration, Oral; D000740:Anemia / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D018925:Chemokines / Q000097:blood; D004195:Disease Models, Animal; D004339:Drug Compounding; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000150:complications / Q000276:immunology / Q000517:prevention & control*; D006403:Hematologic Tests; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053769:Nanocapsules; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018925:Chemokines; D007166:Immunosuppressive Agents; D053769:Nanocapsules; D014230:Triazoles; C030266:3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole