Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis

Arthritis Rheum. 2011 Sep;63(9):2671-80. doi: 10.1002/art.30459.

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 β-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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / drug therapy*
  • Cell Line
  • Cells, Cultured
  • Drug Carriers*
  • Folic Acid / administration & dosage
  • Folic Acid / therapeutic use*
  • Macrophages / drug effects*
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use*
  • Mice
  • Nanoparticles / administration & dosage
  • Nanoparticles / therapeutic use*

Substances

  • Drug Carriers
  • Folic Acid
  • Methotrexate