Joshi, NitinYan, JingLevy, SethBhagchandani, SachinSlaughter, Kai V.Sherman, Nicholas E.Amirault, JulianWang, YufengRiegel, LoganHe, XueyinRui, Tan ShiValic, MichaelVemula, PraveenMiranda, Oscar R.Levy, OrenGravallese, Ellen M.Aliprantis, AntoniosErmann, JoergKarp, Jeffrey2018-05-302018Joshi, N., J. Yan, S. Levy, S. Bhagchandani, K. V. Slaughter, N. E. Sherman, J. Amirault, et al. 2018. “Towards an arthritis flare-responsive drug delivery system.” Nature Communications 9 (1): 1275. doi:10.1038/s41467-018-03691-1. http://dx.doi.org/10.1038/s41467-018-03691-1.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37068159Local 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.en-USJournal Article2018-05-3010.1038/s41467-018-03691-1