Treatment of experimental arthritis with stealth-type polymeric nanoparticles encapsulating betamethasone phosphate

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 329; no. 2; p. 412
• Main Authors: Ishihara, Tsutomu, Kubota, Tetsushi, Choi, Tesu, Higaki, Megumu
• Format: Journal Article
• Language: English
• Published: United States 01-05-2009
• Subjects: Animals; Arthritis, Experimental - drug therapy; Betamethasone - administration & dosage; Betamethasone - analogs & derivatives; Betamethasone - pharmacokinetics; Betamethasone - therapeutic use; Drug Carriers - chemistry; Drug Compounding; Female; Glucocorticoids - administration & dosage; Glucocorticoids - pharmacokinetics; Glucocorticoids - therapeutic use; Injections, Intravenous; Lactic Acid - chemistry; Male; Mice; Mice, Inbred BALB C; Nanoparticles - chemistry; Polyethylene Glycols - chemistry; Polyglycolic Acid - chemistry; Rats; Rats, Inbred Lew; Tissue Distribution; Treatment Outcome
• ISSN: 1521-0103
• DOI: 10.1124/jpet.108.150276

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 microg 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 microg 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.