TY - JOUR T1 - Towards an arthritis flare-responsive drug delivery system. JF - Nat Commun Y1 - 2018 A1 - Joshi, Nitin A1 - Yan, Jing A1 - Levy, Seth A1 - Bhagchandani, Sachin A1 - Slaughter, Kai V A1 - Sherman, Nicholas E A1 - Amirault, Julian A1 - Wang, Yufeng A1 - Riegel, Logan A1 - He, Xueyin A1 - Rui, Tan Shi A1 - Valic, Michael A1 - Vemula, Praveen K A1 - Miranda, Oscar R A1 - Levy, Oren A1 - Gravallese, Ellen M A1 - Aliprantis, Antonios O A1 - Ermann, Joerg A1 - Karp, Jeffrey M AB -

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.

VL - 9 IS - 1 ER -