In vivo evaluation of chondroitin sulfate-glycyl-prednisolone for anti-arthritic effectiveness and pharmacokinetic characteristics

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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 2.5 mg PD equiv./kg × 2 d, CS-GP significantly suppressed swelling of both hind paws, while other preparations were less effective. CS-GP (2.5 mg 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.Graphical abstract

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