Applicability of a Modified Rat Model of Acute Arthritis for Long-Term Testing of Drug Delivery Systems
Imke Rudnik-Jansen,
Nina Woike,
Suzanne de Jong,
Sabine Versteeg,
Marja Kik,
Pieter Emans,
George Mihov,
Jens Thies,
Niels Eijkelkamp,
Marianna Tryfonidou,
Laura Creemers
Affiliations
Imke Rudnik-Jansen
Department of Orthopedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands
Nina Woike
DSM Biomedical B.V., Koestraat 1, 6167 RA Geleen, The Netherlands
Suzanne de Jong
Department of Orthopedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands
Sabine Versteeg
Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
Marja Kik
Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands
Pieter Emans
Department of Orthopaedic Surgery, Research School CAPHRI, Maastricht University Medical Centre, P. Debyelaan, 25, 6229 HX Maastricht, The Netherlands
George Mihov
DSM Biomedical B.V., Koestraat 1, 6167 RA Geleen, The Netherlands
Jens Thies
DSM Biomedical B.V., Koestraat 1, 6167 RA Geleen, The Netherlands
Niels Eijkelkamp
Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
Marianna Tryfonidou
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands
Laura Creemers
Department of Orthopedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands
Episodes of inflammation and pain are predominant features of arthritic joint diseases. Drug delivery systems (DDS) could reduce inflammation and pain long-term without chances of infection upon multiple injections. To allow for long-term evaluation of DDS, we modified a previously published acute arthritis model by extending follow-up periods between flare-ups. Unilateral synovial inflammation of the knee was induced by intra-articular injection of streptococcal cell wall peptidoglycan polysaccharide (PGPS), and flare-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 inflammation of non-primed joints were observed as systemic side effects. To test the applicability of the modified arthritis model for long-term testing of DDS, the duration of anti-inflammatory and analgesic effects of a corticosteroid released from two different polymer-based platforms was evaluated. The current modified 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.
