E. Duizer et al., COMPARISON OF PERMEABILITY CHARACTERISTICS OF THE HUMAN COLONIC CACO-2 AND RAT SMALL-INTESTINAL IEC-18 CELL-LINES, Journal of controlled release, 49(1), 1997, pp. 39-49
Several human colonic carcinoma cell lines are used to study the intes
tinal transport of compounds in vitro. However, the major site of abso
rption of drugs and nutrients is the small intestine, which differs gr
eatly from the colon in paracellular permeability. Several hydrophilic
compounds, of which intestinal uptake in vivo was found, are not tran
sported across filter-grown colonic cells in vitro. The aim of this st
udy was to compare transport properties of the low-resistance rat smal
l intestinal cell line IEC-18 to those of the high-resistance human co
lonic cell line Caco-2. After prolonged culture of Caco-2 and IEC-18 o
n Transwell polycarbonate filters, enzyme activity determinations reve
aled the presence pf sucrase-isomaltase and mature enterocyte alkaline
phosphatase in Caco-2 and fetal alkaline phosphatase in IEC-18. Both
cell lines formed a confluent layer as confirmed by transepithelial el
ectrical resistance measurements (TERCaco-2=350+/-14 Omega.cm(2), TERI
EC-18=55+/-4 Omega.cm(2)) and fluorescence microscopy on immunolabeled
F-actin. The tight junctional protein ZO-1 is organized into cell cir
cumscribing strands in both cell lines. Transport rates of lipophilic
compounds transported transcellularly were almost similar in both cell
lines, but transport rates of hydrophilic compounds transported parac
ellularly were clearly higher in IEC-18 cells. IEC-18 cells also allow
ed for a better discrimination on the basis of molecular size between
several compounds which are transported paracellularly. (C) 1997 Elsev
ier Science B.V.