RT Journal Article
SR Electronic
T1 Treatment of Experimental Arthritis with Stealth-Type Polymeric Nanoparticles Encapsulating Betamethasone Phosphate
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 412
OP 417
DO 10.1124/jpet.108.150276
VO 329
IS 2
A1 Tsutomu Ishihara
A1 Tetsushi Kubota
A1 Tesu Choi
A1 Megumu Higaki
YR 2009
UL http://jpet.aspetjournals.org/content/329/2/412.abstract
AB We examined the therapeutic activity of betamethasone disodium 21-phosphate (BP) encapsulated in biocompatible and biodegradable blended nanoparticles of poly (d,l-lactic/glycolic acid) (PLGA)/poly(d,l-lactic acid) (PLA) homopolymers and polyethylene glycol (PEG)-block-PLGA/PLA copolymers (stealth nanosteroid) in experimental arthritis models. Various stealth nanosteroids with a size of 45 to 115 nm were prepared and then intravenously administered to rats with adjuvant arthritis (AA) rats and mice with anti-type II collagen antibody-induced arthritis (AbIA). The accumulation of stealth nanoparticles with Cy7 in inflamed joints was determined using an in vivo imaging system. The type A stealth nanosteroid, composed of PLA (2.6 kDa) and PEG (5 kDa)-PLA (3 kDa), with a PEG content of 10% and a diameter of 115 nm, exhibited the highest anti-inflammatory activity. In AA rats, a 35% decrease in paw inflammation was obtained in 1 day and maintained for 9 days with a single injection of the type A stealth nanosteroid (40 μg of BP), whereas the same does of nonstealth nanosteroid and 3 times higher free BP showed a significantly weaker response. In AbIA mice, a single injection of the type A stealth nanosteroid (3 μg of BP) resulted in complete remission of the inflammatory response after 1 week. Furthermore, in AbAI mice, the accumulation of type A stealth nanoparticles in inflamed joints was shown to parallel the severity of inflammation. The observed strong therapeutic benefit obtained with the type A stealth nanosteroid in experimental arthritis may have been due to prolonged blood circulation and targeting to the inflamed joint in addition to its sustained release in situ. The American Society for Pharmacology and Experimental Therapeutics