Charge-dependent interaction of self-emulsifying oil formulations with Caco-2 cells monolayers: binding, effects on barrier function and cytotoxicity.
A positively charged self-emulsifying oil formulation (SEOF), aimed to enhance oral bioavailability of drugs poorly soluble in water, was recently developed. In the present study the Caco-2 cell model was used for the investigation of the charge-dependent interactions of this SEOF with human intestinal epithelial cells. The positively charged emulsions affected the barrier properties of the cell monolayer at high concentrations and reduced the cell viability. However, at the dilution with aqueous phase used in the present study (1:2000), the positively charged SEOF did not induce any detectable cytotoxic effect. The binding of the fluorescent dye DiIC(18)(3) was much higher from the positively charged SEOF, compared to the negatively charged formulation, suggesting an increased closer adhesion of the droplets to the cell surface due to the electrostatic attraction. No transepithelial transport of this compound across Caco-2 cell monolayers was observed with any SEOF formulation.
Gershanik
T
T
Department of Pharmaceutics, School of Pharmacy, P.O. Box 12065, The Hebrew University of Jerusalem, 91120, Jerusalem, Israel.
Haltner
E
E
Lehr
C M
CM
Benita
S
S
D000588:Amines / Q000737:chemistry / Q000493:pharmacokinetics; D018938:Caco-2 Cells / Q000378:metabolism*; D003287:Contrast Media / Q000493:pharmacokinetics; D004655:Emulsions / Q000737:chemistry / Q000493:pharmacokinetics*; D019793:Fluorescein / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D009829:Oleic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D055672:Static Electricity; D013696:Temperature
D000588:Amines; D003287:Contrast Media; D004655:Emulsions; D005456:Fluorescent Dyes; D009829:Oleic Acids; D019793:Fluorescein; C033180:ethyl oleate; C008703:oleylamine