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

Wan Uk Kim, Woo Kyoung Lee, Jae Woong Ryoo, Seung Hoon Kim, Jin Kim, Jeehee Youn, So Youn Min, Eui Young Bae, Sue Yun Hwang, Sung Hwan Park, Chul Soo Cho, Jong Sang Park, Ho Youn Kim

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

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 3H-thymidine incorporation assay, respectively. The expression of messenger RNA (mRNA) for transforming growth factor β (TGFβ) and tumor necrosis factor α (TNFα) 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 ∼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 μg 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 μg 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 TGFβ mRNA expression in Peyer's patches, but a lower level of TNFα 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.

Original languageEnglish (US)
Pages (from-to)1109-1120
Number of pages12
JournalArthritis and rheumatism
Volume46
Issue number4
DOIs
StatePublished - Apr 23 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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