Suppression of collagen-induced arthritis by single administration of poly(lactic-co-glycolic acid) nanoparticles entrapping type II collagen: a novel treatment strategy for induction of oral tolerance

Arthritis Rheum. 2002 Apr;46(4):1109-20. doi: 10.1002/art.10198.


Objective: Poly(lactic-co-glycolic acid) (PLGA), a biodegradable polymer, is a carrier for drug delivery systems. This study was undertaken to investigate the tolerogenic effect of single administration of PLGA entrapping type II collagen (CII) on the development of collagen-induced arthritis (CIA).

Methods: The biophysical properties of PLGA nanoparticles entrapping CII (PLGA-CII) were investigated by in vitro release testing of CII, immunohistochemistry analysis, and electron microscopy. PLGA-CII was fed singly to animals 14 days before immunization, and the effect on joint inflammation was assessed. Circulating IgG anti-CII antibodies and T cell responses to CII in draining lymph nodes were assayed by enzyme-linked immunosorbent assay and (3)H-thymidine incorporation assay, respectively. The expression of messenger RNA (mRNA) for transforming growth factor beta (TGFbeta) and tumor necrosis factor alpha (TNFalpha) was determined by reverse transcriptase-polymerase chain reaction.

Results: The in vitro release test showed that CII was slowly discharged from PLGA-CII over a period of a month. After single administration of PLGA-CII, numerous particles approximately 300 nm in size were detectable in Peyer's patches, by electron microscopy and immunohistochemical staining for CII, 14 days after the original feeding. Mice fed a single dose of PLGA containing 40 microg of CII had significantly reduced values for incidence and severity of arthritis, serum IgG anti-CII antibodies, and CII-specific T cell proliferation as compared with mice fed solvent alone, those fed 6 doses of 20 microg CII alone, and those fed a single dose of PLGA alone. PLGA-CII was also able to suppress CIA after disease onset. Moreover, PLGA-CII-fed mice showed a higher level of TGFbeta mRNA expression in Peyer's patches, but a lower level of TNFalpha mRNA expression in draining lymph nodes, compared with the other groups of mice.

Conclusion: Our data show that PLGA may serve as a powerful vehicle to promote the tolerance effect of oral CII and that single administration of PLGA-CII may hold promise as a new treatment strategy in rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / therapy*
  • Arthritis, Rheumatoid / therapy
  • Autoimmunity / drug effects
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology*
  • Cattle
  • Collagen Type II / chemistry*
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression / immunology
  • In Vitro Techniques
  • Lactic Acid / chemistry
  • Lactic Acid / pharmacology*
  • Male
  • Mice
  • Mice, Inbred DBA
  • Microscopy, Electron
  • Particle Size
  • Peyer's Patches / immunology
  • Peyer's Patches / ultrastructure
  • Polyglycolic Acid / chemistry
  • Polyglycolic Acid / pharmacology*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / chemistry
  • Polymers / pharmacology*
  • RNA, Messenger / analysis
  • Transforming Growth Factor beta / genetics
  • Tumor Necrosis Factor-alpha / genetics


  • Biocompatible Materials
  • Collagen Type II
  • Polymers
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid