ABSTRACT
Single-epithelial cell line models of biological barriers, such as the
intestines or the lungs, have long been accepted as in vitro predictors
of in vivo drug permeability. However, these models only reflect an
isolated part of the epithelial barrier, neglecting other cell types
integrated into the tissue in vivo, such as mucus-producing goblet
cells or cells of the innate immune system. Furthermore, these cell
lines represent the normal mucosa with intact tight junctions and
strong barrier properties and do not take into account the patho-
physiological changes happening in the case of inflammation, stress,
or other tissue damage. Thus, they are not suitable to study targeting
of drug delivery systems to diseased tissue or to investigate drug or
drug carrier permeation across the susceptible barrier. Herein we
describe a novel coculture setup of the intestinal mucosa, combining
intestinal epithelial cells with a dendritic and amacrophage cell line,
all three of human origin. The model can be advanced to a repre-
sentative of the susceptible intestinal barrier by induction of inflam-
mation with pro-inflammatory cytokine interleukin-1β. Forty-eight
hours after stimulation, the model demonstrates major pathophysi-
ological changes of the stressed intestinal barrier, such as decreased
barrier function and release of biomarkers of inflammation. Thera-
peutic efficacy of drugs or formulations or possible harmful effects
of xenobiotics can be monitored via measurement of transepithelial
electrical resistance, cytokine measurement, and morphological
investigations using confocal laser scanning microscopy.
