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Addition of Mineral‐Coated Microparticles to Soluble Interleukin‐1 Receptor Antagonist Injected Subcutaneously Improves and Extends Systemic Interleukin‐1 Inhibition
Author(s) -
Clements Anna E. B.,
Leiferman Ellen M.,
Chamberlain Connie S.,
Vanderby Ray,
Murphy William L.
Publication year - 2018
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.201800048
Subject(s) - interleukin 1 receptor antagonist , receptor antagonist , in vivo , antagonist , chemistry , pharmacology , interleukin , interleukin 1 receptor , subcutaneous injection , in vitro , receptor , cytokine , endocrinology , medicine , biochemistry , biology , microbiology and biotechnology
IL‐1 receptor antagonist (IL‐1Ra) inhibits the pro‐inflammatory activity of IL‐1β. However, its short in vivo half‐life and high dose required to inhibit IL‐1β may limit its use in all but a few clinical scenarios. This study examines whether the addition of mineral‐coated microparticles (MPs) to a solution of IL‐1Ra extends its ability to inhibit IL‐1β activity when administered as a subcutaneous injection. MPs efficiently bind proteins in solution and provide sustained protein delivery. In vitro assays demonstrate that IL‐1Ra released from MPs is biologically active and inhibits IL‐1β activity. When MPs are added to an IL‐1Ra solution and injected subcutaneously into a murine model, serum IL‐1Ra is elevated for a longer duration compared to the treatment with the IL‐1Ra solution alone. Further, the addition of MPs to the IL‐1Ra solution results in the inhibition of IL‐1β activity for 7 days. A novel MP formulation that layered IL‐1Ra throughout the coating extends inhibition of IL‐1β activity in vivo for at least 14 days, suggesting potential for long‐term IL‐1β inhibition. Overall addition of MPs to an IL‐1Ra solution injected subcutaneously prolongs the duration of elevated serum concentration of IL‐1Ra and extends its ability to inhibit IL‐1β activity.