Structured polymers enable the sustained delivery of glucocorticoids within the intra-articular space
Author
Crastin, AnaMartin, Claire S
Suresh, Sai
Davies, Scott P
Kearns, Daniel
Parlak, Ahsen
Adcock, Holly
Filer, Andrew
Jones, Simon W
Raza, Karim

Moakes, Richard Ja
Grover, Liam M
Hardy, Rowan S
Affiliation
University of Birmingham; University Hospitals Birmingham NHS Foundation TrustPublication date
2024-12-23
Metadata
Show full item recordAbstract
ntra-articular glucocorticoid injections are effective in controlling inflammation and pain in arthritides but restricted by short duration of action and risk of joint degeneration. Controlled drug release using biocompatible hydrogels offers a unique solution, but limitations of in situ gelation restrict their application. Gellan sheared hydrogels (GSHs) retain the advantages of hydrogels, however their unique microstructures lend themselves to intra-articular application - capable of shear thinning under force but restructuring at rest to enhance residence. This study examined GSHs for extended intra-articular glucocorticoid delivery of prednisolone (10 mg mL-1); demonstrating links between material mechanics, steroid release, and preclinical assessment of efficacy in synoviocyte culture and transgenic(TNF)197Gkl (TNFtg) murine model of arthritis. GSHs demonstrated sustained release, with typical Fickian profiles over 18 days. Moreover, systems showed good stability under extended culture, with inherent cell-compatibility and suppression of inflammatory synoviocyte activation. In TNFtg animals, GSHs suppressed synovitis (70.08%, p < 0.05), pannus formation (45.01%, p < 0.05), and increased articular cartilage (82.23%, p < 0.05) relative to vehicle controls. The extended profile of steroid release from injectable GSH formulations holds promise in the treatment and management of inflammatory arthritides such as rheumatoid and osteoarthritis, representing a step-change in intra-articular drug delivery to suppress long-term joint inflammation.Citation
Crastin A, Martin CS, Suresh S, Davies SP, Kearns D, Parlak A, Adcock H, Filer A, Jones SW, Raza K, Moakes RJ, Grover LM, Hardy RS. Structured Polymers Enable the Sustained Delivery of Glucocorticoids within the Intra-Articular Space. Adv Healthc Mater. 2024 Dec 23:e2403000. doi: 10.1002/adhm.202403000. Epub ahead of print.Type
ArticleAdditional Links
https://onlinelibrary.wiley.com/toc/21922659/0/0PMID
39713898Journal
Advanced Healthcare MaterialsPublisher
Wiley-VCHae974a485f413a2113503eed53cd6c53
10.1002/adhm.202403000