title: In vivo evaluation of chondroitin sulfate-glycyl-prednisolone for anti-arthritic effectiveness and pharmacokinetic characteristics.
abstract: 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.
authors: Department of Drug Delivery Research, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. Electronic address: onishi@hoshi.ac.jp.
authors: Hiraku
authors: H
authors: Onishi
authors: Yusuke
authors: Y
authors: Isoda
authors: Mototaka
authors: M
authors: Matsuyama
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001169:Arthritis, Experimental / Q000188:drug therapy*; D002809:Chondroitin Sulfates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005260:Female; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D002809:Chondroitin Sulfates; D011239:Prednisolone
keywords: Adjuvant-induced arthritis; Anti-inflammatory effect; Chondroitin sulfate-glycyl-prednisolone conjugate; Pharmacokinetic characteristics; Prodrug