{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T21:24:28Z","timestamp":1778707468182,"version":"3.51.4"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T00:00:00Z","timestamp":1549497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Life Science and Health Impulse","award":["40-43100-98-022"],"award-info":[{"award-number":["40-43100-98-022"]}]},{"name":"Reumafonds","award":["LLP22"],"award-info":[{"award-number":["LLP22"]}]},{"name":"Reumafonds","award":["LLP12"],"award-info":[{"award-number":["LLP12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/pharmaceutics11020070","type":"journal-article","created":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T11:50:33Z","timestamp":1549540233000},"page":"70","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Applicability of a Modified Rat Model of Acute Arthritis for Long-Term Testing of Drug Delivery Systems"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2508-3610","authenticated-orcid":false,"given":"Imke","family":"Rudnik-Jansen","sequence":"first","affiliation":[{"name":"Department of Orthopedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Woike","sequence":"additional","affiliation":[{"name":"DSM Biomedical B.V., Koestraat 1, 6167 RA Geleen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8457-3452","authenticated-orcid":false,"given":"Sabine","family":"Versteeg","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marja","family":"Kik","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter","family":"Emans","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Research School CAPHRI, Maastricht University Medical Centre, P. Debyelaan, 25, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Mihov","sequence":"additional","affiliation":[{"name":"DSM Biomedical B.V., Koestraat 1, 6167 RA Geleen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Thies","sequence":"additional","affiliation":[{"name":"DSM Biomedical B.V., Koestraat 1, 6167 RA Geleen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels","family":"Eijkelkamp","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2333-7162","authenticated-orcid":false,"given":"Marianna","family":"Tryfonidou","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1585-3052","authenticated-orcid":false,"given":"Laura","family":"Creemers","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,7]]},"reference":[{"key":"ref_1","first-page":"646","article-title":"Burden of major musculoskeletal conditions","volume":"81","author":"Woolf","year":"2003","journal-title":"Bull. 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