Synergistic effect of antiangiogenic nanotherapy combined with methotrexate in the treatment of experimental inflammatory arthritis.
OBJECTIVE
This study examines the effect of combining the antiangiogenic effect of αvß₃-targeted fumagillin nanoparticles with the conventional antirheumatic drug methotrexate for the treatment of inflammatory arthritis.


METHODS
Arthritis was induced in mice by K/BxN serum transfer, and disease activity was monitored by clinical score and change in ankle thickness. Groups of mice received nanoparticles or methotrexate as single therapy or nanoparticles and methotrexate as combination therapy.


RESULTS
We found that animals treated with a pulse dose of fumagillin nanoparticles followed by methotrexate had significantly improved and sustained clinical response compared with those treated with either agent alone. Histological analysis confirmed a significant decrease in inflammatory cell influx, bone erosions, cartilage damage and angiogenesis with the combination therapy.


CONCLUSIONS
Analysis of plasma cytokine levels suggests that fumagillin nanoparticles enhanced the systemic anti-inflammatory effects of methotrexate. Antiangiogenic nanotherapy may represent a promising approach for the treatment of inflammatory arthritis when combined with a conventional antirheumatic drug.
Zhou
Hui-Fang
HF
Division of Rheumatology, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, MO 63110, USA.
Hu
Grace
G
Wickline
Samuel A
SA
Lanza
Gregory M
GM
Pham
Christine T N
CT
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D050997:Nanomedicine
D020533:Angiogenesis Inhibitors; D008727:Methotrexate