Article Text

Download PDFPDF
Treatment of experimental arthritis with poly(d, l-lactic/glycolic acid) nanoparticles encapsulating betamethasone sodium phosphate
  1. M Higaki1,
  2. T Ishihara2,
  3. N Izumo2,
  4. M Takatsu1,
  5. Y Mizushima2
  1. 1Institute of Medical Science, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki 216-8512, Japan
  2. 2DDS Institute, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato, Tokyo 105-8461, Japan
  1. Correspondence to:
    Professor M Higaki
    Institute of Medical Science, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki 216-8512, Japan;


Objective: To examine the therapeutic activity of hydrophilic glucocorticoid encapsulated in PLGA nanoparticles, which have shown slow release and are targeted to inflamed joints after intravenous administration, in experimental arthritis models.

Methods: Betamethasone sodium phosphate (BSP) encapsulated in PLGA nanoparticles with a size of 100–200 nm (PLGA-nanosteroid) was prepared using a modified oil in water emulsion solvent diffusion method with Zn ions and coated with lecithin. Rats with adjuvant arthritis (AA rats) and mice with anti-type II collagen antibody induced arthritis (AbIA mice) were treated intravenously with PLGA-nanosteroid after the initial sign of arthritis.

Results: In AA rats, a 30% decrease in paw inflammation was obtained in 1 day and maintained for 1 week with a single injection of 100 μg of PLGA-nanosteroid. Soft x ray examination 7 days after this treatment showed decreased soft tissue swelling. Moreover, the PLGA-nanosteroid was also highly effective in AbIA mice. A single injection of 30 μg of the PLGA-nanosteroid resulted in almost complete remission of the inflammatory response after 1 week. In contrast, the same dose of free BSP after three administrations only moderately reduced the severity of inflammation. In addition, a histological examination 7 days after the treatment showed a significant decrease of the inflammatory cells in the joints.

Conclusion: The observed strong therapeutic benefit obtained with PLGA-nanosteroid may be due to the targeting of the inflamed joint and its prolonged release in situ. Targeted drug delivery using a sustained release PLGA-nanosteroid is a successful intervention in experimental arthritis.

  • AA, adjuvant induced arthritis
  • AbIA, antibody induced arthritis
  • BSP, betamethasone sodium phosphate
  • IP, intraperitoneally
  • IV, intravenously
  • LPS, lipopolysaccharide
  • PLA, poly(d, l-lactic acid)
  • PLGA, poly(d, l-lactic/glycolic acid)
  • RA, rheumatoid arthritis
  • poly(d, l-lactic/glycolic acid)
  • nanoparticles
  • betamethasone sodium phosphate
  • adjuvant induced arthritis
  • rats
  • antibody induced arthritis
  • mice

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.