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Semi-permeable coatings fabricated from comb-polymers efficiently protect proteins in vivo

Author

Listed:
  • Mi Liu

    (Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich))

  • Pål Johansen

    (University Hospital Zurich)

  • Franziska Zabel

    (University Hospital Zurich)

  • Jean-Christophe Leroux

    (Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich))

  • Marc A. Gauthier

    (Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich)
    Institut National de la Recherche Scientifique (INRS), EMT Research Center)

Abstract

In comparison to neutral linear polymers, functional and architecturally complex (that is, non-linear) polymers offer distinct opportunities for enhancing the properties and performance of therapeutic proteins. However, understanding how to harness these parameters is challenging, and studies that capitalize on them in vivo are scarce. Here we present an in vivo demonstration that modification of a protein with a polymer of appropriate architecture can impart low immunogenicity, with a commensurably low loss of therapeutic activity. These combined properties are inaccessible by conventional strategies using linear polymers. For the model protein L-asparaginase, a comb-polymer bio-conjugate significantly outperformed the linear polymer control in terms of lower immune response and more sustained bioactivity. The semi-permeability characteristics of the coatings are consistent with the phase diagram of the polymer, which will facilitate the application of this strategy to other proteins and with other therapeutic models.

Suggested Citation

  • Mi Liu & Pål Johansen & Franziska Zabel & Jean-Christophe Leroux & Marc A. Gauthier, 2014. "Semi-permeable coatings fabricated from comb-polymers efficiently protect proteins in vivo," Nature Communications, Nature, vol. 5(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6526
    DOI: 10.1038/ncomms6526
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