Effects of some non-ionic surfactants on transepithelial permeability in Caco-2 cells

The effects of the non-ionic surfactants polysorbate 20, polysorbate 60, po lysorbate 85, cholesteryl poly (24) oxyethylene ether (Solulan C24) and the lanolin-based poly (16) oxyethylene ether (Solulan 16) on the epithelial i ntegrity of monolayers of human intestinal epithelial (Caco-2) cells has be en studied using metformin as a model drug. The aim was to identify the sur factants and their optimal concentrations capable of enhancing drug transpo rt while causing no, or only minor, cellular damage. Effects on cell permea bility were assessed by measurements of the transport of metformin, a hydro philic drug, by monitoring transepithelial electrical resistance. Cell viab ility was determined by the diphenyltetrazolium bromide test (the MTT test) . All the surfactants studied demonstrated concentration-dependent effects on cell permeability and cell viability. The effects on transepithelial elect rical resistance correlated with cell viability, i.e. increased transepithe lial electrical resistance and increased cell-monolayer permeability for me tformin corresponded to decreased cell viability. The results indicate that the Solulan and polysorbate surfactants were active as absorption enhancer s, Solulan C24 and 16 being more effective than polysorbates 20, 60 or 85, causing an increase in metformin transport at lower concentrations than the polysorbates. Polysorbate 20 exerted its greatest effect at a concentratio n of 5%-increasing the flux of metformin after 3h by a factor of around 20 over the control. Large increases in the transport of metformin, especially at surfactant levels of 0.05%, 0.1% and 0.5%, were related to the effect o f Solulan C24 and Solulan 16 on the cell permeability. The Caco-2 cell monolayer experiments confirmed the ability, especially of polysorbate 20, Solulan C24 and Solulan 16, to increase the absorption of m etformin. The polysorbates increased permeability as a result of solubilisa tion of membrane components, while Solulans did so by penetrating and solub ilising the membrane. Correlation between increase in membrane permeability and the toxicity of the surfactants towards the cell membrane has been est ablished.