Intra-articular injection of triamcinolone acetonide releasing biomaterial microspheres inhibits pain and inflammation in an acute arthritis model

Abstract

Inflammation of the synovium and joint capsule is a main driver of pain in an osteoarthritic (OA) joint. Triamcinolone acetonide (TAA) is a classical corticosteroid that reduces synovitis and alleviates pain, albeit transiently. Biomaterial-based local TAA release may prolong the suppression of pain without the need for multiple injections. Polylactic-co-glycolic acid (PLGA) formulations of TAA prolong OA pain relief to a limited extent. A novel polyesteramide (PEA) microsphere platform allows for extended release in the OA joint for over 3 months. To evaluate their effect on pain and inflammation, TAA-loaded microspheres were intra-articularly delivered to the knee joint in a rat model of acute arthritis induced by intra-articular injection of streptococcal cell wall peptidoglycan-polysaccharide (PGPS) and subsequent flare-ups by intravenous PGPS injections. PEA-loaded microspheres were benchmarked with TAA-loaded PLGA microspheres and bolus TAA injection. TAA treatments were injected intra-articularly before the first induced flare-up. TAA-loaded PEA and PLGA microspheres reduced joint swelling and signs of pain-like behavior over the entire study period, as assessed by weight bearing and referred mechanical hypersensitivity, whereas bolus suspension was effective for a shorter time period. TAA-loaded PEA microspheres reduced lameness to a greater extent than TAA-loaded PLGA microspheres. In conclusion, a single intra-articular injection of TAA-loaded PEA microspheres reduced joint swelling and induced longer pain relief compared to bolus injection. Hence relief of inflammation and pain by PEA-based delivery of TAA may prove to be effective and durable.

Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing

“…Possibly, the weight changes between the hind paws were too subtle to detect with a static weight‐bearing measurement device in rats. Other types of analyses previously used for detecting pain in rat studies, such as the von Frey or dynamic weight‐bearing analysis, may be more suitable for measuring pain in future studies (Rudnik‐Jansen, Schrijver, et al, ).…”

Intra-Articular Slow-Release Triamcinolone Acetonide from Polyesteramide Microspheres as a Treatment for Osteoarthritis

“…Polyesteramide polymer ( Figure 1 a) and PEA-loaded microspheres ( Figure 1 b) were synthesized according to previously reported protocols [ 14 , 24 , 41 ] and were also used in a study on effectivity in a rat model [ 12 ]. Briefly, the polymer was prepared via solution polycondensation of di-p-tolue-nesulfonic acid salts of bis-(α-amino acid) α,ω-diol diesters, lysine benzyl ester and di-N-hydroxysuccinimide sebacate in anhydrous DMSO.…”

“…The microspheres used in the current study have been used and characterized in another study published recently [ 25 ]. Release of TA from PEA microspheres in PBS buffer was determined as described before [ 41 ]. Briefly, samples were incubated in a volume of 50 mL at 37 °C, of which 45 mL buffer was renewed.…”

Recent Advances in Clinical Translation of Intra‐Articular Osteoarthritis Drug Delivery Systems

“…This group performed another study comparing PEA and PLGA MPs loaded with TCA. [ 107 ] The mean diameters and TCA loading were 24 versus 39 µm and 28 versus 23% (w/w) for PEA and PLGA, respectively. Rats underwent synovitis flares at days 0, 14, and 28 and received IA injection of empty PEA particles, TCA suspension, PLGA‐TCA, or PEA‐TCA (all 62.5 µg TCA).…”