Towards an arthritis flare-responsive drug delivery system

Nitin Joshi, Jing Yan, Seth Levy, Sachin Bhagchandani, Kai V. Slaughter, Nicholas E. Sherman, Julian Amirault, Yufeng Wang, Logan Riegel, Xueyin He, Tan Shi Rui, Michael Valic, Praveen K. Vemula, Oscar R. Miranda, Oren Levy, Ellen M. Gravallese, Antonios O. Aliprantis, Joerg Ermann () and Jeffrey M. Karp ()
Additional contact information
Nitin Joshi: Brigham and Women’s Hospital
Jing Yan: Harvard Medical School
Seth Levy: Harvard Medical School
Sachin Bhagchandani: Brigham and Women’s Hospital
Kai V. Slaughter: Brigham and Women’s Hospital
Nicholas E. Sherman: Brigham and Women’s Hospital
Julian Amirault: Brigham and Women’s Hospital
Yufeng Wang: Brigham and Women’s Hospital
Logan Riegel: Brigham and Women’s Hospital
Xueyin He: Brigham and Women’s Hospital
Tan Shi Rui: Brigham and Women’s Hospital
Michael Valic: Brigham and Women’s Hospital
Praveen K. Vemula: Brigham and Women’s Hospital
Oscar R. Miranda: Brigham and Women’s Hospital
Oren Levy: Brigham and Women’s Hospital
Ellen M. Gravallese: University of Massachusetts Medical School
Antonios O. Aliprantis: Harvard Medical School
Joerg Ermann: Harvard Medical School
Jeffrey M. Karp: Brigham and Women’s Hospital

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-03691-1

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