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


CONCLUSIONS
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.
Higaki
M
M
Institute of Medical Science, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki 216-8512, Japan. megumu@dd.iij4u.or.jp
Ishihara
T
T
Izumo
N
N
Takatsu
M
M
Mizushima
Y
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001623:Betamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D019344:Lactic Acid; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures; D036103:Nanotechnology / Q000379:methods; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D051381:Rats; D011917:Rats, Inbred Lew
D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005938:Glucocorticoids; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C028994:betamethasone sodium phosphate; D001623:Betamethasone