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Chondroitin sulfate-glycyl-prednisolone conjugate (CS-GP) was previously demonstrated to exhibit superior anti-arthritic effects compared to prednisolone (PD) alone. In this study, CS-GP was examined for its pharmacokinetic features and tropism for inflammatory joints using rats with adjuvant-induced arthritis in order to identify the mechanism of the potential enhancement. After intravenous injection (2.5 mg PD eq./kg), CS-GP yielded an area under the curve (AUC) of the total (free+conjugated) drug much higher than that of PD alone. After intravenous administration at the same dose, the drug distribution to the hind paw inflammatory joints was investigated. For PD alone, the PD concentration was 1.2-1.7 µg/g at 1 h and fell to 0.12-0.14 µg/g at 24 h. In contrast, CS-GP maintained the total concentration in the range of 0.55-0.97 µg/g for 1-24 h, and maintained the free PD concentration at 0.06-0.16 µg/g for 1-24 h. Furthermore, at 24 h after intravenous administration (2.5 mg PD eq./kg), CS-GP exhibited a higher total drug concentration in arthritic rats than in healthy rats. These findings suggested that CS-GP may have the ability to target inflammatory joints. As the apparent molecular weight of CS-GP became greater in plasma, it might interact with blood components and cause high plasma retention and good tropism to the inflammatory sites. Enhancement of the anti-inflammatory potential of CS-GP was found to be due to good maintenance of drug levels in the inflamed area.

Chondroitin Sulfate–Glycyl-Prednisolone Conjugate as Arthritis Targeting System: Localization and Drug Release in Inflammatory Joints