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Structured Polymers Enable the Sustained Delivery of Glucocorticoids within the Intra-Articular Space. | LitMetric

AI Article Synopsis

  • * Gellan sheared hydrogels (GSHs) offer an advanced drug delivery method, maintaining the benefits of hydrogels while providing extended glucocorticoid release and improved stability in the joint environment.
  • * The study found that GSHs not only ensured sustained steroid release over 18 days but also significantly reduced joint inflammation and damage in a murine model of arthritis, indicating their potential for treating conditions like rheumatoid and osteoarthritis.

Article Abstract

Intra-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); 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.

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Source
http://dx.doi.org/10.1002/adhm.202403000DOI Listing

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