Caco-2 cells are the most widely used cell line for predicting intestinal drug absorption as they form polarized monolayers with tight junctions and microvilli like intestinal cells. Other cell lines used include MDCK, HT29-MTX, 2/4/A1, TC-7, LLC-PK1, IEC-18 and T84, but they have limitations such as lack of transporters, unstable monolayers, or poor differentiation. While cell models show good correlation with passive drug permeability, correlations with active transport are more variable. Extensive studies are still needed to fully characterize intestinal drug transport mechanisms in these models.

1. Comparison of Caco-2 with Other Cell-based Models for Intestinal Permeability Stud
info@creative-bioarray.comCreative Bioarray

2. Intestinal Drug Absorption
Cell-based Models for Intestinal Permeability Studies
Intestinal drug absorption is one of the factors that determine
the success of an oral drug product along with its efficacy,
pharmacokinetics, and toxicity. Therefore, models for
predicting intestinal drug absorption are becoming more
important in early drug development to accelerate
identification of promising or troublesome compounds.
The use of cell cultures provides a method to predict drug
permeability by utilizing cell monolayers in a two-chamber
diffusion system to simulate the passage of drugs from the
intestinal lumen into the blood. The cell model is simple and
easy to use and avoids the usage of animal models for
pharmacological and toxicological studies, so it is cost-effective
and can produce reliable and reproducible results for
understanding and evaluating the permeability characteristics
of the potential lead drug candidates.

3. Caco-
2
MDCK
HT29-
MTX
2/4/A
1
TC-7
LLC-
PK1
IEC-
18
T84
Many cell monolayer
models have been
developed to mimic
human intestinal
epithelium and are
gaining in popularity.
These models use
immortalized cells
that grow rapidly
into confluent
monolayers and
undergo spontaneous
differentiation.
Therefore, these cell
monolayer models
provide an ideal
system for the study
of intestinal drug
Cell-based Models for Intestinal Permeability Studies

4. Cell-based Models for Intestinal Permeability Studies
Caco-2 Cell Line
Characteristics
Polarized monolayers with
tight junction, brush
border and apical
microvilli
Expression of some
relevant efflux
transporters
Advantages
Well-developed and
characterized
Good reproducibility,
robustness and functional
property of human
intestinal cells
Origin
Human colon
adenocarcinoma
Limitations
Absence of mucous
secreting goblet cells
Expression of influx
transporters is variable
Not suitable for
paracellular transport
21-days culture period

5. 5
3-5 days culture period
Ideal for transfections
Advantages
Under-expression of major
efflux transporters
Not for active and efflux studies
Not for mechanistic studies
Limitations
Polarized cells with low intrinsic expression of ABC
transporters
Characteristics
Dog kidney
Origin
Cell-based Models for Intestinal Permeability Studies
MDCK Cell Line

6. 6
Advantages
Higher levels of CYP3A4 and 3A5
Useful to evaluate metabolic effects
during transport
Greater homogeneity ensuring more
consistent results with lower variability
Limitations
Similar to Caco-2
Origin
Caco-2 subclone
Characteristics
Low expression of P-gp
Stable expression of CYP3A4
TC7
Cell-based Models for Intestinal Permeability Studies
TC7 Cell Line

7. Human colon carcinoma
Origin
Multilayer of
undifferentiated cells
Lack tight junction &
functional polarity
Characteristics
Contain mucus-producing
goblet cells
Advantages
Not suitable for carrier-
mediated
transport
Unstable mucus layer
Limitations
Cell-based Models for Intestinal Permeability Studies
HT29-MTX Cell Line

8. Origin
Fetal rat intestine
Characteristics
Polarized monolayers with
tight junction, brush border
membrane enzymes and
transporter proteins
Advantages
Temperature-sensitive
Ideal for paracellularly
absorbed compounds (leakier
pores)
Good for medium to low
throughput screening
Limitations
Lack enzyme systems,
transporters fond in Caco-2
and small intestine
Less pharmaceutical use
Cell-based Models for Intestinal Permeability Studies
2/4/A1 Cell Line

9. Advantages
Better model for epithelial permeability study of
hydrophilic molecules than Caco-2
Provides a size-selective barrier for paracellularly
transported compounds
Limitations
Not for cell mediated transport studies
Origin
Rat intestine
Characteristics
Poor cell differentiation
Leakier paracellular pathway
Cell-based Models for Intestinal Permeability Studies
IEC-18 Cell Line
IEC-18

10. Limitations
Not adequate for drug studies and carrier mediated
process
Characteristics
Not well differentiated cells
Advantages
Resemble colonic crypt cell phenotype
Origin
Human colon cancer
Cell-based Models for Intestinal Permeability Studies
T84 Cell Line

11. Cell-based Models for Intestinal Permeability Studies
LLC-PK1 Cell Line
Pig kidney
Polarized cells with low
intrinsic transporter
expression
Characterization of passive
transport
Ideal for transfections
Not for active and efflux
studies
Not for mechanistic studies
Origin Characteristics Advantages Limitations

12. Conclusion
Although all of these cell models show good or moderate
correlations with passively absorbed drug permeability in
humans, correlations with active transport are variable and
mainly low. However, even if in vivo correlation is slow,
they are interesting models for determining drug transport
mechanism, and extensive studies are needed to identify
the relevant carriers and active transport mechanisms.

13. THANKS FOR YOUR ATTENT
info@creative-bioarray.comCreative Bioarray