Abstract
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.
Highlights
Musculoskeletal conditions are the most common cause of severe long-term pain and disability, affecting millions of people worldwide [1]
Joint inflammation is often used to refer to any disorder that affects the joints and the most representative arthritic diseases are osteoarthritis (OA) and rheumatoid arthritis (RA) [1]
The recently developed and characterized polyesteramide (PEA) microsphere platform [9,10] releasing triamcinolone acetonide (TAA) was compared to the poly lactic-co-glycolic acid (PLGA) microsphere platform already evaluated in the original arthritis model [11,12]
Summary
Musculoskeletal conditions are the most common cause of severe long-term pain and disability, affecting millions of people worldwide [1]. In order to better evaluate the duration of analgesic effects of drug delivery systems as primary objective, we adapted the PGPS model of acute arthritis by extending the periods between each reactivation In this adjusted arthritis model, we investigated the anti-inflammatory and analgesic effects of prolonged TAA release from two different drug delivery systems over 84 days. For this purpose, the recently developed and characterized polyesteramide (PEA) microsphere platform [9,10] releasing TAA was compared to the PLGA microsphere platform already evaluated in the original arthritis model [11,12]. Over the course of the prolonged follow-up period, differences in effectiveness of TAA delivery between the PLGA and PEA microsphere platforms were clearly demonstrated as TAA-loaded PEA microspheres were more potent in reducing joint swelling and mechanical hypersensitivity compared to TAA-loaded PLGA microspheres
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