Cell cultures as tools in biopharmacy

Braun, Annette; Hämmerle, Sibylle P.; Suda, Kayoshi; Rothen‐Rutishauser, Barbara; Günthert, Maja; Krämer, Stefanie-Dorothea; Wunderli‐Allenspach, Heidi

doi:10.1016/s0928-0987(00)00164-0

Cited by 137 publications

(77 citation statements)

References 27 publications

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“…It means a higher presence of IONPs in the cell medium and a lower phagocytic activity by carbohydrate-binding proteins as hypothesized in the study by Orlando et al (2014) The internalization of IONPs higher in glioblastoma cells than human urinary bladder carcinoma cells confirm the high invasive ability of this astrocytic tumor. Furthermore, the lower internalization by the ECV304 cell line widely, used in in vitro permeation studies (Braun et al, 2000;Barar et al, 2010;Wang et al, 2011), could suggest an important role of the biological barrier in obstructing the passage of rhamnose-coated IONPs to the brain tumor mass.…”

Section: Discussionmentioning

confidence: 99%

Rhamnose‐coated superparamagnetic iron‐oxide nanoparticles: an evaluation of their in vitro cytotoxicity, genotoxicity and carcinogenicity

Paolini

Guarch

Ramos-López

et al. 2015

J of Applied Toxicology

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Tumor recurrence after the incomplete removal of a tumor mass inside brain tissue is the main reason that scientists are working to identify new strategies in brain oncologic therapy. In particular, in the treatment of the most malignant astrocytic tumor glioblastoma, the use of magnetic nanoparticles seems to be one of the most promising keys in overcoming this problem, namely by means of magnetic fluid hyperthermia (MFH) treatment. However, the major unknown issue related to the use of nanoparticles is their toxicological behavior when they are in contact with biological tissues. In the present study, we investigated the interaction of glioblastoma and other tumor cell lines with superparamagnetic iron-oxide nanoparticles covalently coated with a rhamnose derivative, using proper cytotoxic assays. In the present study, we focused our attention on different strategies of toxicity evaluation comparing different cytotoxicological approaches in order to identify the biological damages induced by the nanoparticles. The data show an intensive internalization process of rhamnose-coated iron oxide nanoparticles by the cells, suggesting that rhamnose moiety is a promising biocompatible coating in favoring cells' uptake. With regards to cytotoxicity, a 35% cell death at a maximum concentration, mainly as a result of mitochondrial damages, was found. This cytotoxic behavior, along with the high uptake ability, could facilitate the use of these rhamnose-coated iron-oxide nanoparticles for future MFH therapeutic treatments.

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Section: Discussionmentioning

confidence: 99%

Rhamnose‐coated superparamagnetic iron‐oxide nanoparticles: an evaluation of their in vitro cytotoxicity, genotoxicity and carcinogenicity

Paolini

Guarch

Ramos-López

et al. 2015

J of Applied Toxicology

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“…• Measure of monolayer integrity • P app of non-absorbable marker • P app of HP and LP markers • Efflux of substrate compound (6,14,19,21,26,48,49) then employed to correctly classify four fluoroquinolone drugs in comparison to known human absorption (40). Ciprofloxacin was classified as a LP drug, while levofloxacin, lomefloxacin, and ofloxacin were classified as HP drugs (40).…”

Section: In Vitro Cell Monolayersmentioning

confidence: 99%

Application of Method Suitability for Drug Permeability Classification

Volpe

2010

AAPS J

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Abstract. Experimental models of permeability in animals, excised tissues, cell monolayers, and artificial membranes are important during drug discovery and development as permeability is one of several factors affecting the intestinal absorption of oral drug products. The utility of these models is demonstrated by their ability to predict a drug's in vivo intestinal absorption. Within the various permeability models, there are differences in the performance of the assays, along with variability in animal species, tissue sources, and cell types, resulting in a variety of experimental permeability values for the same drug among laboratories. This has led to a need for assay standardization within laboratories to ensure applicability in the drug development process. Method suitability provides a generalized approach to standardize and validate a permeability model within a laboratory. First, assay methodology is optimized and validated for its various experimental parameters along with acceptance criteria for the assay. Second, the suitability of the model is demonstrated by a rank order relationship between experimental permeability values and human extent of absorption of known model compounds. Lastly, standard compounds are employed to classify a test drug's intestinal permeability and ensure assay reproducibility and quality. This review will provide examples of the different aspects method suitability for in situ (intestinal perfusions), ex vivo (everted intestinal sacs, diffusion chambers), and in vitro (cell monolayers, artificial membranes) experimental permeability models. Through assay standardization, reference standards, and acceptance criteria, method suitability assures the dependability of experimental data to predict a drug's intestinal permeability during discovery, development, and regulatory application.KEY WORDS: artificial membranes; drug permeability; ex vivo perfusion; in situ perfusion; in vitro cell monolayers; method suitability.

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“…Caco-2 cells were obtained from human colon adenocarcinoma cells; they could differentiate into monolayers that both structurally and functionally resemble the small intestinal epithelium (22). The transcript level of MRP2 in Caco-2 was comparable to its level in human jejunum of the small intestine, which is the major site for oral drug absorption (23). In addition, MRP2 transcript level in both Caco-2 cells and jejunum is much higher than MDR1 and other MRP transporters (24).…”

Section: Introductionmentioning

confidence: 99%

Effects of Monoglycerides on Rhodamine 123 Accumulation, Estradiol 17 β-D-Glucuronide Bidirectional Transport and MRP2 Protein Expression within Caco-2 cells

Jia

2008

J Pharm Pharm Sci

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-Purpose. Oral drug development had been hindered by the bioavailability issue despite vast market popularity. Lipid excipients had shown to enhance bioavailability of a number of reformulated hydrophobic oral drugs, yet the underlying mechanisms of action by lipids are still unclear. One proposed mechanism is that lipid excipients could facilitate drug uptake by altering the activities of apical membrane intestinal efflux transporters. Thus, this study aimed to investigate the effects of 1-monopalmitin, 1-monoolein and 1-monostearin on the efflux activity and protein expression of multidrug resistance-associated protein 2 (MRP2) in vitro. Methods. The 24-hour non-cytotoxic ranges of these monoglycerides were first determined using MTS and LDH assays in Caco-2 cells. Then, both accumulation and bidirectional transport studies were conducted using 10 μM rhodamine 123 (Rh123) and 10 nM estradiol 17 β-D-glucuronide (E 2 17βG), respectively, to assess the functional activities of MRP2. 50 µM MK-571, a specific MRP1 and MRP2 inhibitor, was used as the positive control in both studies. Western blotting was followed to determine the effect of these monoglycerides on MRP2 protein expression. Results. Caco-2 cells were viable when treated with 1-monopalmitin, 1-monostearin and 1-monoolein at concentrations equal or less than 1000 µM, 1000 µM and 500 µM, respectively. Cells treated with 1-monoplamitin, 1-monostearin, 1-monoolein and MK571 resulted in significant increases in Rh123 accumulation and decreases in E 2 17βG efflux ratio compared to the control (medium treated only). MRP2 protein expressions in 1-monopalmitin and 1-monoolein treated cells were decreased by 19% and 35% compared to the control; however, there was no change of MRP2 protein expression in 1-monostearin treated cells. Conclusions. These findings suggested that 1-monoolein, 1-monostearin and 1-monopalmitin could attenuate the activity of MRP2 and possibly other efflux transporters in Caco-2 cells. The reduction of efflux activity of MRP2 by 1-monoolein treatment could be partially accounted by the non-specific down-regulation of MRP2 protein expression.

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Cell cultures as tools in biopharmacy

Cited by 137 publications

References 27 publications

Rhamnose‐coated superparamagnetic iron‐oxide nanoparticles: an evaluation of their in vitro cytotoxicity, genotoxicity and carcinogenicity

Rhamnose‐coated superparamagnetic iron‐oxide nanoparticles: an evaluation of their in vitro cytotoxicity, genotoxicity and carcinogenicity

Application of Method Suitability for Drug Permeability Classification

Effects of Monoglycerides on Rhodamine 123 Accumulation, Estradiol 17 β-D-Glucuronide Bidirectional Transport and MRP2 Protein Expression within Caco-2 cells

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