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Treatment of experimental arthritis with poly(D, L-lactic/glycolic acid) nanoparticles encapsulating betamethasone sodium phosphate

M Higaki¹, T Ishihara², N Izumo², M Takatsu¹, Y Mizushima²

¹ Institute of Medical Science, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki 216-8512, Japan
² DDS Institute, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato, Tokyo 105-8461, Japan

Correspondence to:
Professor M Higaki
Institute of Medical Science, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki 216-8512, Japan; megumu{at}dd.iij4u.or.jp

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.

Abbreviations: 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

Keywords: poly(d, l-lactic/glycolic acid); nanoparticles; betamethasone sodium phosphate; adjuvant induced arthritis; rats; antibody induced arthritis; mice

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• Ishihara, T., Kubota, T., Choi, T., Higaki, M. (2009). Treatment of Experimental Arthritis with Stealth-Type Polymeric Nanoparticles Encapsulating Betamethasone Phosphate. J. Pharmacol. Exp. Ther. 329: 412-417 [Abstract] [Full Text]