Injectable biomaterials for delivery of interleukin-1 receptor antagonist: Toward improving its therapeutic effect

Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring anti-inflammatory cytokine that inhibits IL-1 activity and has been proposed to treat a wide variety of systemic and local inflammatory pathologies for multiple decades. However, the short half-life and high concentration required to inhibit IL-I activity has limited its use in clinical applications. Many strategies have been developed with the goal of improving the therapeutic efficacy of IL-1Ra for a variety of pathologies, including fusing IL-1Ra to protein/peptide/polymer partners, releasing 1L-1Ra from injectable polymer or mineral particles, and release of IL-1Ra from injectable coacervates and gels. This literature review examines injectable biomaterials engineered to improve IL-1Ra delivery, both locally and systemically, to increase its efficacy and ease of use in clinic. Statement of Significance Interleukin-1 receptor antagonist (IL-1Ra) is a therapeutic protein with the potential to treat numerous inflammatory conditions and diseases. However, its short biological half-life and high therapeutic concentration may limit its utility in all but a few clinical scenarios. In this review, we present the biomaterial based delivery strategies which have been explored to deliver IL-1Ra to improve its efficacy and applicability to treat inflammation. (C) 2019 Published by Elsevier Ltd on behalf of Acta Materialia Inc.