Online citations, reference lists, and bibliographies.
← Back to Search

Cell Cultures As Tools In Biopharmacy.

A. Braun, S. Hämmerle, K. Suda, B. Rothen-Rutishauser, M. Guenthert, S. Krämer, H. Wunderli-Allenspach
Published 2000 · Medicine, Chemistry

Cite This
Download PDF
Analyze on Scholarcy
A survey is given on a few selected cell culture models that are used for transport studies. They are characterised for growth, transcellular electrical resistance and cytoarchitecture. The importance of standardisation in view of their use as transport models is documented. Their potential for studies on passive permeation and P-glycoprotein-mediated transport is explored and related to published data. Transport studies are presented that were performed in a two-chamber set-up, the Costar "vertical diffusion system". A series of non-homologous compounds showed similar permeability data (P(app)) in the different cell cultures. The origin of the cell type had no remarkable influence on passive transcellular permeation. MDCK cells, an epithelial cell line of canine kidney origin, are perfectly suited to screen for passive permeation. They have low expression of transporter proteins and low metabolic activity. In general, they probably represent the best-known epithelial cell line with respect to genetics as well as lipid and protein composition. MDCK cells are easy to handle. Transport experiments can be done between 7 and 14 days after seeding, when the stationary growth phase is reached. To screen for P-glycoprotein substrates, efflux and uptake studies were performed with mdr1-transfected MDCK cells (MDR1-MDCK) in a one-chamber system in the presence or absence of verapamil or cyclosporin A as inhibitor. Evidence is presented why the transfected cells, which express large amounts of P-glycoprotein, are not suitable for two-chamber transport studies.
This paper references
Substituent constants for correlation analysis in chemistry and biology
C. Hansch (1979)
Properties of an immortalised vascular endothelial/glioma cell co‐culture model of the blood‐brain barrier
R. D. Hurst (1996)
The Blood-brain Barrier and Drug Delivery to the CNS
D. Begley (2000)
Development of a new physicochemical model for brain penetration and its application to the design of centrally acting H2 receptor histamine antagonists.
R. C. Young (1988)
Functional characterization of the spontaneously transformed human umbilical vein endothelial cell line ECV304: use in an in vitro model of angiogenesis.
S. Hughes (1996)
Ex vivo maintenance of differentiated mammalian cells.
L. Reid (1997)
Physicochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes.
M. Kansy (1998)
Functionally Differentiated Cell Lines
K. Sikora (1982)
Absorption prediction from physicochemical parameters.
Kraemer (1999)
ECV304 (endothelial) is really T24 (bladder carcinoma): Cell line cross-contamination at source
Wilhelm G. Dirks (1999)
Upregulation of intercellular adhesion molecule-1 expression on human endothelial cells by tumour necrosis factor-α in an in vitro model of the blood–brain barrier
M. Dobbie (1999)
MDCK (Madin-Darby canine kidney) cells: A tool for membrane permeability screening.
J. D. Irvine (1999)
P-Glycoprotein (P-gp) mediated efflux in Caco-2 cell monolayers: the influence of culturing conditions and drug exposure on P-gp expression levels.
P. Anderle (1998)
Identification of two strains of MDCK cells which resemble separate nephron tubule segments.
J. C. Richardson (1981)
Kinetics of the multidrug transporter (P-glycoprotein) and its reversal.
W. Stein (1997)
Use of rhodamine 123 to examine the functional activity of P-glycoprotein in primary cultured brain microvessel endothelial cell monolayers.
M. Fontaine (1996)
Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells.
P. Artursson (1991)
High glucose concentrations inhibit glucose phosphorylation, but not glucose transport, in human endothelial cells.
F. Viñals (1999)
The Development of In Vitro Models for the Blood–Brain and Blood–CSF Barriers
D. Korte (2000)
Transepithelial transport of drugs by the multidrug transporter in cultured Madin-Darby canine kidney cell epithelia.
M. Horio (1989)
Positively cooperative sites for drug transport by P-glycoprotein with distinct drug specificities.
A. Shapiro (1997)
Development of Caco-2 Cells Expressing High Levels of cDNA-Derived Cytochrome P4503A4
C. Crespi (2004)
MDCK Cell Cultures as an Epithelial In Vitro Model: Cytoskeleton and Tight Junctions as Indicators for the Definition of Age-Related Stages by Confocal Microscopy
B. Rothen-Rutishauser (2004)
Cytochrome P-450 3A4: regulation and role in drug metabolism.
F. Guengerich (1999)
Predicting blood-brain barrier permeation from three-dimensional molecular structure.
P. Crivori (2000)
P-Glycoprotein in cell cultures: a combined approach to study expression, localisation, and functionality in the confocal microscope.
S. Hämmerle (2000)
A retrovirus carrying an MDR1 cDNA confers multidrug resistance and polarized expression of P-glycoprotein in MDCK cells.
I. Pastan (1988)
Polarized monolayers formed by epithelial cells on a permeable and translucent support
M. Cereijido (1978)

This paper is referenced by
In vitro and in vivo testing methods for respiratory drug delivery
R. Agu (2011)
The egress of fluid from the brain via arachnoid transport: foundational work for the tissue engineering of the arachnoid granulation
Cornelius H. Lam (2011)
Alternatives to Conventional Toxicology Testing
Joseph Bressler (2010)
The anticancer potential of CITme, a quinoline derivative
S. Martins (2011)
IPEC-J2 rMdr1a, a New Cell Line with Functional Expression of Rat P-glycoprotein Encoded by Rat Mdr1a for Drug Screening Purposes
L. Saaby (2020)
Elucidating the Signal Responses of Multi-Parametric Surface Plasmon Resonance Living Cell Sensing: A Comparison between Optical Modeling and Drug–MDCKII Cell Interaction Measurements
T. Viitala (2013)
CNS Drug Disposition : The Relationship Between In Situ Brain Permeability and Brain Free Fraction
S. Summerfield (2007)
Excretory Processes in Toxicology: Drug Transporters in Drug Development
Kp. Van Ness (2018)
Investigation of vesicle electrokinetic chromatography as an in vitro assay for the estimation of intestinal permeability of pharmaceutical drug candidates
R. Pascoe (2006)
Why we should be vigilant: drug cytotoxicity observed with in vitro transporter inhibition studies.
Xiaowan Zheng (2010)
Development of novel fluorine-18 labeled PET tracers for imaging of the metabotropic glutamate receptor subtype 5 (mGluR5)
C. A. Baumann (2010)
A Modified Coumarinic Acid-Based Cyclic Prodrug of an Opioid Peptide: Its Enzymatic and Chemical Stability and Cell Permeation Characteristics
H. Ouyang (2004)
Challenges and opportunities for tissue-engineering polarized epithelium.
C. PazAna (2014)
Effect of transmembrane potential on the diffusion of Na⁺/H⁺ exchanger of human red blood cell
A. Pasula (2010)
Drug Absorption Studies
C. Ehrhardt (2008)
Genomic Knockout of Endogenous Canine P-Glycoprotein in Wild-Type, Human P-Glycoprotein and Human BCRP Transfected MDCKII Cell Lines by Zinc Finger Nucleases
Dominik Gartzke (2014)
Development of an in Vitro Rat Intestine Segmental Perfusion Model to Investigate Permeability and Predict Oral Fraction Absorbed
Marc-Etienne Castella (2006)
Decision trees to characterise the roles of permeability and solubility on the prediction of oral absorption.
D. Newby (2015)
Investigation of the transport of lipophilic drugs in structurally diverse lipid formulations through caco-2 cell monolayer using mathematical modeling
M. Schneider (2008)
Current industrial practices of assessing permeability and P-glycoprotein interaction
P. Balimane (2008)
Central Nervous System Drug Disposition: The Relationship between in Situ Brain Permeability and Brain Free Fraction
S. Summerfield (2007)
Effect of the modulation of the membrane lipid composition on the localization and function of P-glycoprotein in MDR1-MDCK cells
S. Kamau (2005)
Interplay of Passive and Active Drug Disposition in in vitro Models of Drug Absorption and Distribution
A. Heikkinen (2010)
In Vitro Screening Models to Assess Intestinal Drug Absorption and Metabolism
S. Deferme (2008)
Handbook of Preformulation: Chemical, Biological, and Botanical Drugs
S. Niazi (2006)
Cell culture methods for acute toxicology testing
F. Barile (2013)
Intestinal transport of HDND-7, a novel hesperetin derivative, in in vitro MDCK cell and in situ single-pass intestinal perfusion models
Ruonan Chen (2017)
Crude plant extract versus single compounds for vitiligo treatment: Ex vivo intestinal permeability assessment on Brosimum gaudichaudii Trécul.
R. Machado (2020)
In vitro adhesion assays for probiotics and their in vivo relevance: a review
A. Ouwehand (2003)
ECV304/C6 coculture model of the BBB coupled with LC–MS analysis for drug screening from Rhubarb extract
J. Yuan (2016)
Ocular permeability screening of dexamethasone esters through combined cellular and tissue systems.
C. Civiale (2004)
Immortalization and functional characterization of rat arachnoid cell lines
C. Janson (2011)
See more
Semantic Scholar Logo Some data provided by SemanticScholar