Dr. Wan-Uk Kim and Woo-Kyoung Lee contributed equally to this work.
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
Article first published online: 5 APR 2002
Copyright © 2002 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 46, Issue 4, pages 1109–1120, April 2002
How to Cite
Kim, W.-U., Lee, W.-K., Ryoo, J.-W., Kim, S.-H., Kim, J., Youn, J., Min, S.-Y., Bae, E.-Y., Hwang, S.-Y., Park, S.-H., Cho, C.-S., Park, J.-S. and Kim, H.-Y. (2002), 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 & Rheumatism, 46: 1109–1120. doi: 10.1002/art.10198
- Issue published online: 5 APR 2002
- Article first published online: 5 APR 2002
- Manuscript Accepted: 26 NOV 2001
- Manuscript Received: 4 SEP 2001
- Ministry of Health and Welfare of the Republic of South Korea. Grant Number: HMP-98-G-2-039
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).
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.
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.
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.