Kiss, Lóránd and Walter, Fruzsina and Bocsik, Alexandra and Veszelka, Szilvia and Ózsvári, Béla and Puskás, László and Révész, Piroska and Deli, Mária Anna (2013) Kinetic analysis of the toxicity of Cremophor EL and RH40 on endothelial and epithelial cells. Journal of Pharmaceutical Sciences, 102 (4). pp. 1173-1181. ISSN 0022-3549
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Abstract
Cremophor EL and RH40 are widely used excipients in oral and intravenous drug formulations such as Taxol infusion to improve drug dissolution and absorption. Studies indicate that Cremophors, especially EL, have toxic side effects, but few data are available on endothelial and epithelial cells, which form biological barriers and are directly exposed to these molecules. Human hCMEC/D3 brain endothelial and Caco-2 epithelial cells were treated with Cremophor EL and RH40 in the 0.1–50 mg/mL concentration range. Cell toxicity was monitored by real-time cell microelectronic sensing and verified by lactate dehydrogenase release and 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and morphological methods. Cremophors caused dose- and time-dependent damage in both cell types. In endothelial cells, 0.1 mg/mL and higher concentrations, in epithelial cells, concentrations of 5 mg/mL and above were toxic, especially at longer incubations. Cell death was also proven by double fluorescent staining of cell nuclei. Immunostaining for tight junction proteins claudin-4 and -5 showed barrier disruption in cells treated by surfactants at 24 h. In conclusion, Cremophor EL and RH40 in concentrations corresponding to clinical doses caused endothelial and epithelial toxicity. Endothelial cells were more sensitive to surfactant treatment than epithelial cells, and Cremophor EL was more toxic than RH40 in both cell types. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1173–1181, 2013
Item Type: | Article |
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Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia |
SWORD Depositor: | MTMT SWORD |
Depositing User: | MTMT SWORD |
Date Deposited: | 08 Nov 2013 07:37 |
Last Modified: | 08 Nov 2013 07:37 |
URI: | http://real.mtak.hu/id/eprint/7188 |
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