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 studies using the hydrophilic markers (mannitol, polyethylene glycols (PEGS) 900 and 4000) indicated that the paracellular permeability of the co-culture model was greater than that of the CaCo-2 model. At pH 7.4, no difference in the transport of a model lipophilic drug, dextropropoxyphene, was observed between the two models. However, at pH 4.5, when the drug was highly ionised the transport was significantly lower across the co-culture monolayers. NaTC micellar systems appeared to affect the different cell culture models in the order CaCo-2>CaCo-2-Ht29GlucH>Ht29GlucH. Following removal of the 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.
Meaney
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Leiden/Amsterdam Centre for Drug Research, Division of Pharmaceutical Technology, 2300RA, Leiden, Netherlands.
O'Driscoll
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D000042:Absorption; D001692:Biological Transport; D018938:Caco-2 Cells; D018920:Coculture Techniques; D011431:Dextropropoxyphene / Q000378:metabolism; D017097:Electric Impedance; D020397:Goblet Cells / Q000166:cytology; D006801:Humans; D008823:Micelles; D008854:Microscopy, Electron; D009077:Mucins / Q000378:metabolism*; D010539:Permeability; D013656:Taurocholic Acid / Q000737:chemistry
D008823:Micelles; D009077:Mucins; D013656:Taurocholic Acid; D011431:Dextropropoxyphene