| Cytotoxicity study of ordered mesoporous silica MCM-41 and SBA-15 microparticles on Caco-2 cells. | |
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MedLine Citation:
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PMID: 20025968 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cytotoxicity of ordered mesoporous silica MCM-41 and SBA-15 microparticles (fractions between 1 and 160 microm) was determined in vitro on undifferentiated human colon carcinoma (Caco-2) cell line, considering the feasibility of using these silica-based materials in oral drug formulations. The cellular endpoints employed for assessing the effects of the MCM-41 and SBA-15 microparticles on Caco-2 were: (1) cell membrane integrity by monitoring live-cell protease activity (AFC) and by employing the flow cytometry method; (2) metabolic activity by monitoring total ATP content via luminescence assay; (3) activity of apoptotic effectors by caspase-3/7 activity assay. The generation of reactive oxygen species (ROS) was also followed, specifically the hydrogen peroxide (H(2)O(2)) and the superoxide radical (O(2)(-)). MCM-41 and SBA-15 microparticles caused cytotoxic effects on the Caco-2 cells, at most tested concentrations (0.2-14 mg/ml) and incubation times (3 and 24h). The effects on the cells included weakened cell membrane integrity, diminished cell metabolism and increased apoptotic signalling. The root cause for the cytotoxicity was heightened production of reactive oxygen species (ROS), especially the formation of the superoxide radical O(2)(-) already after 3h incubation with threshold dose 1mg/ml, apparently overwhelming the antioxidant defences and causing mitochondrial dysfunction, hence increasing the apoptotic signalling. |
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Authors:
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Teemu Heikkil?; H?lder A Santos; Narendra Kumar; Dmitry Yu Murzin; Jarno Salonen; Timo Laaksonen; Leena Peltonen; Jouni Hirvonen; Vesa-Pekka Lehto |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-16 |
Journal Detail:
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Title: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft f?r Pharmazeutische Verfahrenstechnik e.V Volume: 74 ISSN: 1873-3441 ISO Abbreviation: Eur J Pharm Biopharm Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-08 Completed Date: 2010-06-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9109778 Medline TA: Eur J Pharm Biopharm Country: Netherlands |
Other Details:
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Languages: eng Pagination: 483-94 Citation Subset: IM |
Copyright Information:
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(c) 2009 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Physics and Astronomy, University of Turku, Turku, Finland. teemu.heikkila@utu.fi |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Caco-2 Cells Caspase 3 / metabolism Caspase 7 / metabolism Cell Survival / drug effects Drug Carriers / chemistry, pharmacology* Flow Cytometry Humans Microscopy, Electron, Scanning Particle Size Porosity Reactive Oxygen Species / metabolism Silicon Dioxide / chemistry, pharmacology* Surface Properties |
| Chemical | |
Reg. No./Substance:
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0/Drug Carriers; 0/MCM-41; 0/Reactive Oxygen Species; 0/SBA-15; 7631-86-9/Silicon Dioxide; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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