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Towards an arthritis flare-responsive drug delivery system

Author

Listed:
  • Nitin Joshi

    (Brigham and Women’s Hospital
    Massachusetts Institute of Technology
    Harvard Medical School)

  • Jing Yan

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • Seth Levy

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • 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
    Massachusetts Institute of Technology
    Harvard Medical School
    UAS-GKVK post)

  • Oscar R. Miranda

    (Brigham and Women’s Hospital
    Massachusetts Institute of Technology
    Harvard Medical School)

  • Oren Levy

    (Brigham and Women’s Hospital
    Massachusetts Institute of Technology
    Harvard Medical School)

  • Ellen M. Gravallese

    (University of Massachusetts Medical School)

  • Antonios O. Aliprantis

    (Harvard Medical School
    Brigham and Women’s Hospital
    Merck Research Laboratories)

  • Joerg Ermann

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • Jeffrey M. Karp

    (Brigham and Women’s Hospital
    Massachusetts Institute of Technology
    Harvard Medical School)

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.

Suggested Citation

  • 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. , 2018. "Towards an arthritis flare-responsive drug delivery system," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03691-1
    DOI: 10.1038/s41467-018-03691-1
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