Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis.
Arthritis Rheum
; 63(9): 2671-80, 2011 Sep.
Article
em En
| MEDLINE
| ID: mdl-21618461
ABSTRACT
OBJECTIVE:
To investigate the uptake of a poly(amidoamine) dendrimer (generation 5 [G5]) nanoparticle covalently conjugated to polyvalent folic acid (FA) as the targeting ligand into macrophages, and to investigate the activity of an FA- and methotrexate (MTX)-conjugated dendrimer (G5-FA-MTX) as a therapeutic for the inflammatory disease of arthritis.METHODS:
In vitro studies were performed in macrophage cell lines and in isolated mouse macrophages to check the cellular uptake of fluorescence-tagged G5-FA nanoparticles, using flow cytometry and confocal microscopy. In vivo studies were conducted in a rat model of collagen-induced arthritis to evaluate the therapeutic potential of G5-FA-MTX.RESULTS:
Folate-targeted dendrimer bound and internalized in a receptor-specific manner into both folate receptor ß-expressing macrophage cell lines and primary mouse macrophages. The conjugate G5-FA-MTX acted as a potent antiinflammatory agent and reduced arthritis-induced parameters of inflammation such as ankle swelling, paw volume, cartilage damage, bone resorption, and body weight decrease.CONCLUSION:
The use of folate-targeted nanoparticles to specifically target MTX into macrophages may provide an effective clinical approach for antiinflammatory therapy in rheumatoid arthritis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Experimental
/
Portadores de Fármacos
/
Metotrexato
/
Nanopartículas
/
Ácido Fólico
/
Macrófagos
Limite:
Animals
Idioma:
En
Revista:
Arthritis Rheum
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos