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Effect of Rhamnolipids on Permeability Across Caco-2 Cell Monolayers

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ABSTRACT

Purpose

This report describes the effect of rhamnolipids (RLs), an amphiphilic biosurfactant produced by the bacterium Pseudomonas aeruginosa, on the integrity and permeability across Caco-2 cell monolayers.

Methods

We measured the trans-epithelial electrical resistance (TEER) and permeability of [14C]mannitol across Caco-2 cell monolayers upon incubation with 0.01–5.0% v/v RLs as a function of incubation time (30, 60, 90, and 120 min). We also studied the recovery of RL-treated Caco-2 cell monolayers upon incubation with Kaempferol, which is a natural flavonoid that promotes the assembly of the tight junctions.

Results

TEER of Caco-2 cell monolayers incubated with 0.01–5.0% v/v RLs solution dropped to 80–28% of that of untreated cells. Decline in TEER was associated with an increase in [14C]mannitol permeability as a function of RLs concentration and incubation time with Caco-2 cells. Incubation of RLs-treated Caco-2 cell monolayers with normal culture medium for 48 h did not restore barrier integrity. Whereas, incubation of a RLs-treated Caco-2 cells with culture medium containing Kaempferol for 24 h restored barrier function indicated by the higher TEER and lower [14C]mannitol permeability values.

Conclusions

These results show the ability of RLs to modulate the integrity and permeability of Caco-2 cell monolayers in a concentration- and time-dependent fashion, which suggest their potential to function as a non-toxic permeation enhancer.

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ACKNOWLEDGMENTS AND DISCLOSURES

Charity J. Wallace and Scott H. Medina contributed equally to this research.

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Authors and Affiliations

  1. Department of Biomedical Engineering Cellular Engineering & Nano-Therapeutics Laboratory College of Engineering, University of Michigan, Ann Arbor, Michigan, 48109, USA

    Charity J. Wallace, Scott H. Medina & Mohamed E. H. ElSayed

  2. Macromolecular Science and Engineering Program, University of Michigan, Ann Arbor, Michigan, 48109, USA

    Mohamed E. H. ElSayed

  3. Department of Biomedical Engineering, University of Michigan, 1101 Beal Avenue, Lurie Biomedical Engineering Building, Room 2150, Ann Arbor, Michigan, 48109, USA

    Mohamed E. H. ElSayed

Authors
  1. Charity J. Wallace
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  2. Scott H. Medina
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  3. Mohamed E. H. ElSayed
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Correspondence to Mohamed E. H. ElSayed.

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Wallace, C.J., Medina, S.H. & ElSayed, M.E.H. Effect of Rhamnolipids on Permeability Across Caco-2 Cell Monolayers. Pharm Res 31, 887–894 (2014). https://doi.org/10.1007/s11095-013-1210-5

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  • DOI: https://doi.org/10.1007/s11095-013-1210-5

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