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 language | English (US) |
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Pages (from-to) | 1109-1120 |
Number of pages | 12 |
Journal | Arthritis and rheumatism |
Volume | 46 |
Issue number | 4 |
DOIs | |
State | Published - 2002 |
ASJC Scopus subject areas
- Immunology and Allergy
- Rheumatology
- Immunology
- Pharmacology (medical)