Effect of rhamnolipids on permeability across Caco-2 cell monolayers

Pharm Res. 2014 Apr;31(4):887-94. doi: 10.1007/s11095-013-1210-5. Epub 2013 Sep 25.

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 [(14)C]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 [(14)C]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 [(14)C]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.

MeSH terms

  • Caco-2 Cells
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / physiology*
  • Glycolipids / metabolism*
  • Glycolipids / pharmacology*
  • Humans
  • Kaempferols / pharmacology
  • Permeability / drug effects
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism*

Substances

  • Glycolipids
  • Kaempferols
  • rhamnolipid
  • kaempferol