In vivo evaluation of chondroitin sulfate-glycyl-prednisolone for anti-arthritic effectiveness and pharmacokinetic characteristics.
A conjugate between chondroitin sulfate (CS) and glycyl-prednisolone (GP), named CS-GP, was prepared as a delivery system for the treatment of rheumatoid arthritis by referring to the previous report. CS-GP conjugates with different prednisolone (PD) contents of 1.4, 2.0 and 4.3% (w/w) were obtained, and their conversion characteristics were investigated at 37 °C under pH 6 and 7.4. Release profiles were similar among the conjugates, being slow at pH 6 (24 h: 9-14%), and fairly fast at pH 7.4 (7 h: 46-58%). CS-GP, PD, CS and the PD/CS mixture were investigated for anti-inflammatory effects by i.v. administration to rats with adjuvant-induced arthritis. At 2.5mg PD equiv./kg×2 d, CS-GP significantly suppressed swelling of both hind paws, while other preparations were less effective. CS-GP (2.5mg PD equiv./kg×2 d) tended to be more effective than PD (5 mg/kg×2 d). Change in body weight indicated that CS-GP was not toxic. After i.v. injection in normal rats, CS-GP showed much higher plasma levels than PD alone, and organ accumulation of CS-GP was not observed. CS-GP was suggested to be possibly useful for the treatment of rheumatoid arthritis.
['Onishi|Hiraku|H|', 'Isoda|Yusuke|Y|', 'Matsuyama|Mototaka|M|']
D000818:Animals D000893:Anti-Inflammatory Agents D001169:Arthritis, Experimental D002809:Chondroitin Sulfates D016503:Drug Delivery Systems D005260:Female D008297:Male D011239:Prednisolone D051381:Rats D011917:Rats, Inbred Lew D017208:Rats, Wistar
Pharmacokinetic characteristics Anti-inflammatory effect Adjuvant-induced arthritis Chondroitin sulfate-glycyl-prednisolone conjugate Prodrug