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Nat Commun. 2018 Apr 3;9(1):1275. doi: 10.1038/s41467-018-03691-1.

Towards an arthritis flare-responsive drug delivery system.

Author information

1
Center for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
2
Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
3
Harvard Medical School, Boston, MA, 02115, USA.
4
Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
5
Institute for Stem Cell Biology and Regenerative Medicine (inStem), UAS-GKVK post, Bellary Road, Bangalore, 560065, India.
6
Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
7
Merck Research Laboratories, 33 Ave Louis Pasteur, Boston, MA, 02115, USA.
8
Harvard Medical School, Boston, MA, 02115, USA. jermann@bwh.harvard.edu.
9
Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA. jermann@bwh.harvard.edu.
10
Center for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA. jmkarp@bwh.harvard.edu.
11
Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. jmkarp@bwh.harvard.edu.
12
Harvard Medical School, Boston, MA, 02115, USA. jmkarp@bwh.harvard.edu.

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.

PMID:
29615615
PMCID:
PMC5882944
DOI:
10.1038/s41467-018-03691-1
[Indexed for MEDLINE]
Free PMC Article

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