Division of Rheumatology, Department of Medicine
Biomedical Devices and Instrumentation | Immune System Diseases | Macromolecular Substances | Musculoskeletal Diseases | Pathological Conditions, Signs and Symptoms | Rheumatology | Therapeutics
Local delivery of therapeutics for the treatment of inflammatory arthritis (IA) is limited by short intra-articular half-lives. Since IA severity often fluctuates over time, a local drug delivery method that titrates drug release to arthritis activity would represent an attractive paradigm in IA therapy. Here we report the development of a hydrogel platform that exhibits disassembly and drug release controlled by the concentration of enzymes expressed during arthritis flares. In vitro, hydrogel loaded with triamcinolone acetonide (TA) releases drug on-demand upon exposure to enzymes or synovial fluid from patients with rheumatoid arthritis. In arthritic mice, hydrogel loaded with a fluorescent dye demonstrates flare-dependent disassembly measured as loss of fluorescence. Moreover, a single dose of TA-loaded hydrogel but not the equivalent dose of locally injected free TA reduces arthritis activity in the injected paw. Together, our data suggest flare-responsive hydrogel as a promising next-generation drug delivery approach for the treatment of IA.
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© The Author(s) 2018. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
Nat Commun. 2018 Apr 3;9(1):1275. doi: 10.1038/s41467-018-03691-1. Link to article on publisher's site
Joshi, Nitin; Gravallese, Ellen M.; Ermann, Joerg; and Karp, Jeffrey M., "Towards an arthritis flare-responsive drug delivery system" (2018). Open Access Articles. 3458.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Biomedical Devices and Instrumentation Commons, Immune System Diseases Commons, Macromolecular Substances Commons, Musculoskeletal Diseases Commons, Pathological Conditions, Signs and Symptoms Commons, Rheumatology Commons, Therapeutics Commons