title: Effect of the non-ionic surfactant Poloxamer 188 on passive permeability of poorly soluble drugs across Caco-2 cell monolayers.
abstract: Drug permeability of the model drugs ketoprofen and nadolol across Caco-2 cell monolayers was determined in the absence and presence of the non-ionic surfactant Poloxamer 188 (Pluronic® F68, P-188). Stringent controls confirmed that P-188 in concentrations up to 50 mg/ml did not adversely affect cell viability or monolayer integrity. Equilibrium experiments confirmed that the drugs were merely passively transported. Caco-2 permeability of both drugs was found to be decreased by the surfactant in a concentration-dependent manner. Ultrafiltration revealed that both drugs were associated with surfactant micelles. The systematic investigation of micellization on passive absorption showed that association of drugs with P-188 micelles appears to depress their passive permeability under conditions where other transport mechanisms can be neglected.
authors.affiliation: Department of Physics and Chemistry, University of Southern Denmark, Odense, Denmark. smf@ifk.sdu.dk
authors.forename: Sarah Maud
authors.initials: SM
authors.lastname: Fischer
authors.forename: Martin
authors.initials: M
authors.lastname: Brandl
authors.forename: Gert
authors.initials: G
authors.lastname: Fricker
mesh_terms: D000042:Absorption / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D007660:Ketoprofen / Q000493:pharmacokinetics; D008823:Micelles; D009248:Nadolol / Q000493:pharmacokinetics; D010539:Permeability / Q000187:drug effects; D020442:Poloxamer / Q000494:pharmacology*; D012995:Solubility; D013501:Surface-Active Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014462:Ultrafiltration / Q000379:methods
chemical_list: D008823:Micelles; D013501:Surface-Active Agents; D020442:Poloxamer; D009248:Nadolol; D007660:Ketoprofen