Efficacy of a nanocochleate-encapsulated 3,5-diaryl-s-triazole derivative in a murine model of graft-versus-host disease.
Transplantation
; 86(1): 171-5, 2008 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-18622296
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Triazoles
/
Enfermedad Injerto contra Huésped
/
Inmunosupresores
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Transplantation
Año:
2008
Tipo del documento:
Article
País de afiliación:
Italia