Effect of different surfactants in biorelevant medium on the secretion of a lipophilic compound in lipoproteins using Caco-2 cell culture.
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.
Karpf
Ditte M
DM
Department of Pharmaceutics, The Danish University of Pharmaceutical Sciences, DK-2100 Copenhagen, Denmark.
Holm
René
R
Garafalo
Carole
C
Levy
Emile
E
Jacobsen
Jette
J
Müllertz
Anette
A
D018938:Caco-2 Cells; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D019301:Oleic Acid / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D011136:Polysorbates / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology*; D014801:Vitamin A / Q000378:metabolism*
D008074:Lipoproteins; D008244:Lysophosphatidylcholines; D011136:Polysorbates; D013501:Surface-Active Agents; D014801:Vitamin A; D019301:Oleic Acid; C022131:cremophor; D011092:Polyethylene Glycols