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

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.

• Authors: Thommey P Thomas, Sascha N Goonewardena, Istvan J Majoros, Alina Kotlyar, Zhengyi Cao, Pascale R Leroueil, James R Baker Jr
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 63 Issue 9 Pg. 2671-80 (Sep 2011) ISSN: 1529-0131 [Electronic] United States
• PMID: 21618461 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 by the American College of Rheumatology.

Chemical References

• Drug Carriers
• Folic Acid
• Methotrexate

Topics

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