Kinetic Analysis of the Toxicity of Pharmaceutical Excipients Cremophor EL and RH40 on Endothelial and Epithelial Cells

Kiss, Lóránd; Walter, Fruzsina R.; Bocsik, Alexandra; Veszelka, Szilvia; Ózsvári, Béla; Puskás, László G.; Szabó‐Révész, Piroska; Deli, Mária A.

doi:10.1002/jps.23458

Cited by 97 publications

(94 citation statements)

References 29 publications

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“…Accordingly, the cytotoxicity of PASP matrices was investigated by XTT and LDH tests [7,19]. The negative control, which consisted of the culture medium diluted two-fold with sterile PBS, showed 100% cellular viability ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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Supermacroporous chemically cross-linked poly(aspartic acid) hydrogels

et al. 2015

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a b s t r a c tChemically cross-linked poly(aspartic acid) (PASP) gels were prepared by a solid-liquid phase separation technique, cryogelation, to achieve a supermacroporous interconnected pore structure. The precursor polymer of PASP, polysuccinimide (PSI) was cross-linked below the freezing point of the solvent and the forming crystals acted as templates for the pores. Dimethyl sulfoxide was chosen as solvent instead of the more commonly used water. Thus larger temperatures could be utilized for the preparation and the drawback of increase in specific volume of water upon freezing could be eliminated. The morphology of the hydrogels was characterized by scanning electron microscopy and interconnectivity of the pores was proven by the small flow resistance of the gels. Compression tests also confirmed the interconnected porous structure and the complete re-swelling and shape recovery of the supermacroporous PASP hydrogels. The prepared hydrogels are of interest for several biomedical applications as scaffolding materials because of their cytocompatibility, controllable morphology and pH-responsive character.

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Section: Resultsmentioning

confidence: 99%

“…Cytotoxicity and viability tests were made on human intestinal epithelial Caco-2 cells [19]. The PBS solutions in which the PASP hydrogels were swollen during sterilization were used in the biological tests.…”

Section: Characterizationmentioning

confidence: 99%

Supermacroporous chemically cross-linked poly(aspartic acid) hydrogels

et al. 2015

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“…This result was also corroborated by the cell morphology after exposure (Figure 3) when we used the ANC (nanoemulsion control) made only with water and surfactant. The cytotoxicity of Cremophor EL has already been described for endothelial and epithelial cells, using the MTT test, with the endothelial cells being more sensitive than the epithelial cells [35]. Cremophor, similar to other surfactants, has a profound influence on cell membranes.…”

Section: Discussionmentioning

confidence: 98%

Andiroba Oil (Carapa guianensis Aublet) Nanoemulsions: Development and Assessment of Cytotoxicity, Genotoxicity, and Hematotoxicity

Milhomem-Paixão

Fascineli

Muehlmann

et al. 2017

Journal of Nanomaterials

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Andiroba oil (AO) is obtained from an Amazonian plant and is used in traditional medicine. We carried out a comparative study to test the cytotoxicity, genotoxicity, and hematotoxicity of the oil and its nanoemulsion (AN) in vitro (fibroblasts, lineage NIH/3T3) and in vivo (Swiss mice). The AN was characterized by DLS/Zeta, and its stability was investigated for 120 days. The biological activity of AN was assessed in vitro by MTT test and cell morphology analyses and in vivo by micronucleus, comet, and hematotoxicity tests. The AN presented a hydrodynamic diameter (Hd) of 142.5 ± 3.0 and PDI of 0.272 ± 0.007 and good stability at room temperature. The MTT test evidenced the cytotoxicity of AO and of AN only at their highest concentrations, but AN showed lower cytotoxicity than AO. A lower cytotoxicity of AN, when compared to AO, is in fact an interesting data suggesting that during therapeutic application there will be a lower impact in the cell viability of healthy cells. Cytotoxicity, genotoxicity, and hematotoxicity were not observed in vivo. These tests on the biological and toxicological effects of andiroba oil and nanostructured oil are still initial ones but will give a direction to future application in cosmetics and/or the development of new phytotherapics.

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“…Confluent monolayers of adherent epithelial or endothelial cells grown on culture inserts are widely used static models for intestinal, lung and blood-brain barriers (BBB). The Caco-2 human epithelial cell line is a well characterized model of the intestinal barrier applied for screening of drug candidates [3][4][5][6]. Several studies describe the lung epithelial cell line A549 as a model of the lung barrier [7,8].…”

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A versatile lab-on-a-chip tool for modeling biological barriers

Walter

Valkai

Kincses

et al. 2016

Sensors and Actuators B: Chemical

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Keywords: Microfluidics Lung and intestinal epithelial cells Endothelial cells Blood-brain barrier PermeabilityTrans-epithelial/endothelial electric resistance a b s t r a c t Models of biological barriers are important to study physiological functions, transport mechanisms, drug delivery and pathologies. However, there are only a few integrated biochips which are able to monitor several of the crucial parameters of cell-culture-based barrier models. The aim of this study was to design and manufacture a simple but versatile device, which allows a complex investigation of barrier functions. The following functions and measurements are enabled simultaneously: co-culture of 2 or 3 types of cells; flow of culture medium; visualization of the entire cell layer by microscopy; real-time transcellular electrical resistance monitoring; permeability measurements. To this end, a poly(dimethylsiloxane)-based biochip with integrated transparent gold electrodes and with a possibility to connect to a peristaltic pump was built. Unlike previous systems, the structure of the device allowed a constant visual observation of cell growth over the whole membrane surface. Morphological characterization of the layers was also accomplished by immunohistochemical staining. The chip was applied to monitor and characterize models of the intestinal and lung epithelial barriers, and the blood-brain barrier. The models were established using human Caco-2 intestinal and A549 lung epithelial cell lines, hCMEC/D3 human brain endothelial cell line and primary rat brain endothelial cells co-cultured with primary astrocytes and brain pericytes. This triple primary co-culture blood-brain barrier model was assembled on a lab-on-a-chip device and investigated under fluid flow for the first time. Such a versatile tool is expected to facilitate the kinetic investigation of various biological barriers.

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Kinetic Analysis of the Toxicity of Pharmaceutical Excipients Cremophor EL and RH40 on Endothelial and Epithelial Cells

Cited by 97 publications

References 29 publications

Supermacroporous chemically cross-linked poly(aspartic acid) hydrogels

Supermacroporous chemically cross-linked poly(aspartic acid) hydrogels

Andiroba Oil (Carapa guianensis Aublet) Nanoemulsions: Development and Assessment of Cytotoxicity, Genotoxicity, and Hematotoxicity

A versatile lab-on-a-chip tool for modeling biological barriers

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