Effects of Cosolvents, Bile Acids, and Other Surfactants

Effects of Cosolvents, Bile Acids, and other Surfactants 

Yamashita et al. [33] added up to 10 mM taurocholic acid (cmc 2.9 mM), cholic acid (cmc 2.5 mM), or sodium lauryl sulfate (SLS, low ionic strength cmc 8.2 mM) to the donating solutions in Caco-2 assays. Although the two bile acids did not interfere in the transport of dexamethasone, SLS caused the Caco-2 cell junctions to become leakier, even at the sub-cmc 1 mM level. The permeability of dexamethasone was also decreased at 10 mM SLS. 

These general observations have been confirmed in PAMPA measurements in our laboratory, using the 2% DOPC-dodecane lipid. With very lipophilic molecules, glycocholic acid added to the donor solution slightly reduced permeabilities, taurocholic acid increased permeabilities, but SLS arrested membrane transport altogether in several cases (especially cationic, surface-active drugs such as CPZ). 

Yamashita et al. [82] tested the effect of PEG400, DMSO, and ethanol, with up to 10% added to solutions in Caco-2 assays. PEG400 caused a dramatic decrease (75%) in the permeability of dexamethasone at 10% cosolvent concentration DMSO caused a 50% decrease, but ethanol had only a slight decreasing effect. 

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