Macromolecular Ester Prodrug of Prednisolone with Chondroitin Sulfate for the Treatment of Rheumatoid Arthritis

This paper introduces a drug delivery system candidate for the treatment of rheumatoid arthritis (RA). It was designed as a conjugate between prednisolone (PD) and chondroitin sulfate (CS) via a glycine linker. The obtained conjugate, named CS-GP was examined for the property and feasibility as the DDS for the treatment of RA. First, the release characteristics were investigated under different pH conditions. PD was released directly from CS-GP, it was gradually released at physiological pH (pH 7.4), and more slowly regenerated at acidic RA conditions (pH 6 – 7.3). The efficacy was evaluated using rats with adjuvant-induced arthritis. CS-GP suppressed the swelling of the joints more than PD alone and the mixture of PD and CS, which indicated that the conjugate improved the efficacy of PD. The pharmacokinetic analysis using normal rats exhibited the well-retained manner of CS in blood circulation, and organ distribution was small with i.v. injection of CS-GP. Furthermore, CS-GP showed higher localization to the inflammatory joints than normal ones, which supported that CS-GP should have a targeting potential to the inflammatory sites. These resultant physicochemical characteristics, biological functions and pharmacokinetic features of CS-GP demonstrated the possible usefulness of CS-GP as an anti-arthritic delivery system.