Applicability of a Modi_ed Rat Model of Acute Arthritis for Long-Term Testing of Drug Delivery Systems

Authors
I Rudnik-Jansen, N Woike, S de Jong, S Versteeg et al

Lab
Department of Orthopedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherland

Journal
Pharmaceutics

Abstract
Episodes of in_ammation and pain are predominant features of arthritic joint diseases. Drug delivery systems (DDS) could reduce in_ammation and pain long-term without chances of infection upon multiple injections. To allow for long-term evaluation of DDS, we modi_ed a previously published acute arthritis model by extending follow-up periods between _are-ups. Unilateral synovial in_ammation of the knee was induced by intra-articular injection of streptococcal cell wall peptidoglycan polysaccharide (PGPS), and _are-ups were induced by intravenous PGPS injections every 4 weeks for a total duration of 84 days. In PGPS-reactivated animals, joint swelling, pain behavior, post mortem synovitis, and osteophyte formation were notable features. Hepatitis, splenitis and in_ammation of non-primed joints were observed as systemic side effects. To test the applicability of the modi_ed arthritis model for long-term testing of DDS, the duration of anti-in_ammatoryandanalgesiceffectsofacorticosteroidreleasedfromtwodifferentpolymer-based platforms was evaluated. The current modi_ed arthritis model has good applicability for testing of DDS for a prolonged period of time. Furthermore, the novel autoregulatory polyesteramide (PEA) microsphere platform releasing triamcinolone acetonide (TAA) was benchmarked against poly lactic-co-glycolic acid (PLGA) and reduced joint swelling and pain behavior more potently compared to TAA-loaded PLGA microspheres.

BIOSEB Instruments Used:
Dynamic Weight Bearing 2.0 (BIO-DWB-DUAL)