Effect of different surfactants in biorelevant medium on the secretion of a lipophilic compound in lipoproteins using Caco-2 cell culture

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Ditte M Karpf, René Holm, Carole Garafalo, Emile Levy, Jette Jacobsen, Anette Müllertz

The impact of a pharmaceutical relevant metabolizable, ionic surfactant or two synthetic, nonionic surfactants on the absorption and lipoprotein incorporation of a lipophilic drug, retinol, was studied in the Caco-2 cell culture. Filter-grown monolayers of Caco-2 cells were incubated for 20 h with (3)H-retinol and (14)C-oleic acid and with increasing concentrations of lyso-phosphatidylcholine (lyso-PC), Cremophor RH40, or Tween 80. The concentration of (3)H-retinol and (14)C-lipid was measured in the apical, intracellular, and basolateral compartments. The basolateral medium was ultracentrifugated into different lipoprotein classes and their (3)H-retinol and (14)C-lipid concentrations were determined. The cells incubated with lyso-PC and Tween 80 increased the incorporation of (3)H-retinol and (14)C-lipid into chylomicrons and very low density lipoproteins (VLDL). The explored surfactants impacted the incorporation of (3)H-retinol and (14)C-lipid in chylomicrons and VLDL in a concentration-dependent manner. As these surfactants interfere with the intestinal lipoprotein secretion, inclusion of high concentrations of the surfactants in lipid-based formulations of poorly aqueous soluble drugs might impact the degree of intestinal lymphatic transport of the drug after oral administration.
Original languageEnglish
JournalJournal of Pharmaceutical Sciences
Volume95
Issue number1
Pages (from-to)45-55
Number of pages10
ISSN0022-3549
DOIs
Publication statusPublished - 2006

Bibliographical note

Keywords: Caco-2 Cells; Humans; Lipoproteins; Lysophosphatidylcholines; Oleic Acid; Polyethylene Glycols; Polysorbates; Surface-Active Agents; Vitamin A

ID: 9010613