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.
| Original language | English |
|---|---|
| Pages (from-to) | 171-175 |
| Number of pages | 5 |
| Journal | Transplantation |
| Volume | 86 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 15 2008 |
Fingerprint
Keywords
- CD62L
- Chemokines
- Graft-versus-host disease
- ST1959 3 5-Diaryl-s-triazole
ASJC Scopus subject areas
- Transplantation
- Immunology
Cite this
Efficacy of a nanocochleate-encapsulated 3,5-diaryl-s-triazole derivative in a murine model of graft-versus-host disease. / Campo, Silvia; Arseni, Brunilde; Rossi, Stefania; D'Alessio, Valeria; Lu, Ruying; Ngoje, Joel; Ahl, Patrick L.; Bonitz, Susan; Mannino, Raphael; Di Mitri, Diletta; Battistini, Luca; Carminati, Paolo; De Santis, Rita; Ruggiero, Vito.
In: Transplantation, Vol. 86, No. 1, 15.07.2008, p. 171-175.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Efficacy of a nanocochleate-encapsulated 3,5-diaryl-s-triazole derivative in a murine model of graft-versus-host disease
AU - Campo, Silvia
AU - Arseni, Brunilde
AU - Rossi, Stefania
AU - D'Alessio, Valeria
AU - Lu, Ruying
AU - Ngoje, Joel
AU - Ahl, Patrick L.
AU - Bonitz, Susan
AU - Mannino, Raphael
AU - Di Mitri, Diletta
AU - Battistini, Luca
AU - Carminati, Paolo
AU - De Santis, Rita
AU - Ruggiero, Vito
PY - 2008/7/15
Y1 - 2008/7/15
N2 - 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.
AB - 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.
KW - CD62L
KW - Chemokines
KW - Graft-versus-host disease
KW - ST1959 3 5-Diaryl-s-triazole
UR - http://www.scopus.com/inward/record.url?scp=49849104757&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=49849104757&partnerID=8YFLogxK
U2 - 10.1097/TP.0b013e31817ba761
DO - 10.1097/TP.0b013e31817ba761
M3 - Article
VL - 86
SP - 171
EP - 175
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 1
ER -