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Polyphenol-stabilized coacervates for enzyme-triggered drug delivery

Author

Listed:
  • Wonjun Yim

    (University of California San Diego)

  • Zhicheng Jin

    (University of California San Diego)

  • Yu-Ci Chang

    (University of California San Diego)

  • Carlos Brambila

    (University of California San Diego)

  • Matthew N. Creyer

    (University of California San Diego)

  • Chuxuan Ling

    (University of California San Diego)

  • Tengyu He

    (University of California San Diego)

  • Yi Li

    (University of California San Diego)

  • Maurice Retout

    (University of California San Diego)

  • William F. Penny

    (University of California San Diego)

  • Jiajing Zhou

    (University of California San Diego)

  • Jesse V. Jokerst

    (University of California San Diego
    University of California San Diego
    University of California San Diego)

Abstract

Stability issues in membrane-free coacervates have been addressed with coating strategies, but these approaches often compromise the permeability of the coacervate. Here we report a facile approach to maintain both stability and permeability using tannic acid and then demonstrate the value of this approach in enzyme-triggered drug release. First, we develop size-tunable coacervates via self-assembly of heparin glycosaminoglycan with tyrosine and arginine-based peptides. A thrombin-recognition site within the peptide building block results in heparin release upon thrombin proteolysis. Notably, polyphenols are integrated within the nano-coacervates to improve stability in biofluids. Phenolic crosslinking at the liquid-liquid interface enables nano-coacervates to maintain exceptional structural integrity across various environments. We discover a pivotal polyphenol threshold for preserving enzymatic activity alongside enhanced stability. The disassembly rate of the nano-coacervates increases as a function of thrombin activity, thus preventing a coagulation cascade. This polyphenol-based approach not only improves stability but also opens the way for applications in biomedicine, protease sensing, and bio-responsive drug delivery.

Suggested Citation

  • Wonjun Yim & Zhicheng Jin & Yu-Ci Chang & Carlos Brambila & Matthew N. Creyer & Chuxuan Ling & Tengyu He & Yi Li & Maurice Retout & William F. Penny & Jiajing Zhou & Jesse V. Jokerst, 2024. "Polyphenol-stabilized coacervates for enzyme-triggered drug delivery," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51218-8
    DOI: 10.1038/s41467-024-51218-8
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    References listed on IDEAS

    as
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