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Macro- and Microrheological Properties of Mucus Surrogates in Comparison to Native Intestinal and Pulmonary Mucus

  • Benedikt C. Huck
    Benedikt C. Huck
    Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI)  and  Department of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany
  • Olga Hartwig
    Olga Hartwig
    Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI)  and  Department of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany
    More by Olga Hartwig
  • Alexander Biehl
    Alexander Biehl
    Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University, D-66123 Saarbruecken, Germany
  • Konrad Schwarzkopf
    Konrad Schwarzkopf
    Department of Anesthesia and Intensive Care, Klinikum Saarbrücken gGmbH, 66123 Saarbruecken, Germany
  • Christian Wagner
    Christian Wagner
    Experimental Physics, Saarland University, 66123 Saarbruecken, Germany
  • Brigitta Loretz
    Brigitta Loretz
    Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University, D-66123 Saarbruecken, Germany
  • Xabier Murgia*
    Xabier Murgia
    Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University, D-66123 Saarbruecken, Germany
    *E-mail: [email protected] (X.M.).
  • , and 
  • Claus-Michael Lehr*
    Claus-Michael Lehr
    Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI)  and  Department of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany
    *E-mail: [email protected] (C.-M.L.).
Cite this: Biomacromolecules 2019, 20, 9, 3504–3512
Publication Date (Web):August 16, 2019
https://doi.org/10.1021/acs.biomac.9b00780
Copyright © 2019 American Chemical Society

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    Abstract

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    Mucus is a complex hydrogel that acts as a protective barrier in various parts of the human body. Both composition and structural properties play a crucial role in maintaining barrier properties while dictating diffusion of molecules and (nano)materials. In this study, we compare previously described mucus surrogates with the native human airway and pig intestinal mucus. Oscillatory shear rheology was applied to characterize mucus on the bulk macrorheological level, revealing that the artificial airway surrogate deviates from the elastic-dominant behavior of native mucus samples. We circumvented this limitation through the addition of a cross-linking polymer to the surrogate, adjusting the rheological properties closer to those of native mucus. Applying particle tracking microrheology, we further demonstrated that the mechanical properties at the microscale differ significantly between artificial and native mucus. We conclude that proper characterization of mucus and its surrogates is vital for a reliable investigation of nanoparticle-based mucosal drug delivery.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.biomac.9b00780.

    • Representative strain-sweep experiments to determine the linear-viscoelastic region; individual oscillatory measurements of native mucus and artificial surrogates; oscillatory measurements of samples containing 0.5% and increasing concentrations of PAA; shear rate versus viscosity of water and art-AirM showing increasing viscosity values at lower shear rates when approaching the rheometer detection limit; standard calibration curve of mucin quantification; and mucin concentrations for native mucus samples determined by PAS assay (PDF)

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