SFEBES2023 Poster Presentations Metabolism, Obesity and Diabetes (70 abstracts)
Developing flare-responsive intra-articular steroid injections
Ana Crastin 1 , Claire S. Martin 2 , Michael Sagmeister 1 , Holly V. Adcock 3 , Holly R. Adams 4 , Karim Raza 4 , Andrew Filer 4 , Richard J. A. Moakes 3 , Liam M. Grover 3 & Rowan S. Hardy 1
1IMSR, University of Birmingham, Birmingham, United Kingdom. 2University of Oxford, Oxford, United Kingdom. 3ITM, University of Birmingham, Birmingham, United Kingdom. 4IIA, University of Birmingham, Birmingham, United Kingdom
Intra-articular (IA) glucocorticoids (GCs) injections are effective in controlling joint inflammation but limited by short duration of action and off-target side effects. Gellan sheared hydrogels (SHs) area drug delivery vehicle, with unique thinning properties and enhanced release kinetics. We hypothesise that a combination of SHs and pre-receptor metabolism activated GCs provide slow-release drug delivery to target inflammation and minimise side-effects. We the release kinetics of GC loaded SHs and examined their IA application in a murine model of polyarthritis. SHs containing either vehicle, active prednisolone (10 mg/ml) and metabolism activated prednisone (10 mg/ml) were generated under shear gelling conditions. Steroid release properties in vitro over time were examined by ELISA. GCs loaded SHs, vehicle loaded control or GC only were examined in the TNFtg model of polyarthritis after IA injection(10ul) of animals at six weeks. After 21 days, animals were culled, and measures of disease activity, joint inflammation score, body weight and joint histology were examined. GC hydrogels released steroids in vitro for 12 days, whereas the neat GC was detectable for 48 h by ELISA. The IA injection visualisation was done using a dyed hydrogel. IA Gel injection was tolerated with irritation or tissue break down. No changes were detected in body weight, global disease, and inflammatory paw scores in treated animals. Histological knee analysis has shown that synovitis and pannus(P≤0.001) were reduced in Prednisolone gel group and cartilage was preserved in the Active/Inactive GC gel(P≤0.05) groups compared to control and vehicle injected groups. GC delivery by gellan sheared hydrogels were well tolerated by intra-articular injection. Prednisolone hydrogel showed effective suppression of joint destruction in TNFtg mice relative to standard solution and reduced synovitis and collagen loss. However, metabolism activated gels failed to show efficacy relative to Prednisolone gels in vivo.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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