Mucus as a barrier to the permeability of hydrophilic and lipophilic compounds in the absence and presence of sodium taurocholate micellar systems using cell culture models

A mucus secreting CaCo-2-Ht29GlucH cell co-culture model was characterised and used to examine the influence of mucus as a barrier to the transport of hydrophilic and lipophilic compounds in the absence and presence of sodium taurocholate micellar (NaTC) systems. TEER measurements and permeability s tudies using the hydrophilic marlrers (mannitol, polyethylene glycols (PEGS ) 900 and 4000) indicated that the paracellular permeability of the co-cult ure model was greater than that of the CaCo-2 model. At pH 7.4, no differen ce in the transport of a model lipophilic drug, dextropropoxyphene, was obs erved between the two models. However, at pH 4.5, when the drug was highly ionised the transport was significantly lower across the co-culture monolay ers. NaTC micellar systems appeared to affect the different cell culture mo dels in the order CaCo-2>CaCo-2-Ht29GlucH>Ht29GlucH. Following removal of t he mucus layer by incubation with the mucolytic agent, N-acetyl-L-cysteine, the absorption enhancing potential of NaTC micellar systems was increased in the co-culture model. (C) 1999 Elsevier Science B.V. All rights reserved .