Cytotoxicity study of ordered mesoporous silica MCM-41 and SBA-15 microparticles on Caco-2 cells
Cytotoxicity of ordered mesoporous silica MCM-41 and SBA-15 microparticles (fractions between 1 and 160 μm) 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...
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| Veröffentlicht in: | European journal of pharmaceutics and biopharmaceutics 2010-03, Vol.74 (3), p.483-494 |
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| container_title | European journal of pharmaceutics and biopharmaceutics |
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| creator | Heikkilä, Teemu Santos, Hélder A. Kumar, Narendra Murzin, Dmitry Yu Salonen, Jarno Laaksonen, Timo Peltonen, Leena Hirvonen, Jouni Lehto, Vesa-Pekka |
| description | Cytotoxicity of ordered mesoporous silica MCM-41 and SBA-15 microparticles (fractions between 1 and 160
μm) 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
2O
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 24
h). 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 3
h incubation with threshold dose 1
mg/ml, apparently overwhelming the antioxidant defences and causing mitochondrial dysfunction, hence increasing the apoptotic signalling. |
| doi_str_mv | 10.1016/j.ejpb.2009.12.006 |
| format | Article |
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μm) 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
2O
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 24
h). 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 3
h incubation with threshold dose 1
mg/ml, apparently overwhelming the antioxidant defences and causing mitochondrial dysfunction, hence increasing the apoptotic signalling.</description><identifier>ISSN: 0939-6411</identifier><identifier>EISSN: 1873-3441</identifier><identifier>DOI: 10.1016/j.ejpb.2009.12.006</identifier><identifier>PMID: 20025968</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Biocompatibility ; Biological and medical sciences ; Caco-2 ; Caco-2 Cells ; Caspase 3 - metabolism ; Caspase 7 - metabolism ; Cell Survival - drug effects ; Cell viability ; Cytotoxicity ; Drug Carriers - chemistry ; Drug Carriers - pharmacology ; Flow Cytometry ; General pharmacology ; Humans ; Medical sciences ; Mesoporous silica ; Microparticle ; Microscopy, Electron, Scanning ; Oral drug delivery ; Particle Size ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Porosity ; Reactive Oxygen Species - metabolism ; Silicon Dioxide - chemistry ; Silicon Dioxide - pharmacology ; Surface Properties</subject><ispartof>European journal of pharmaceutics and biopharmaceutics, 2010-03, Vol.74 (3), p.483-494</ispartof><rights>2009 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>(c) 2009 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-d11f9fe2235fa1a63ac863595fac9121134826a3bc4ff5fb040d8bb1028b27583</citedby><cites>FETCH-LOGICAL-c418t-d11f9fe2235fa1a63ac863595fac9121134826a3bc4ff5fb040d8bb1028b27583</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejpb.2009.12.006$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22586706$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20025968$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heikkilä, Teemu</creatorcontrib><creatorcontrib>Santos, Hélder A.</creatorcontrib><creatorcontrib>Kumar, Narendra</creatorcontrib><creatorcontrib>Murzin, Dmitry Yu</creatorcontrib><creatorcontrib>Salonen, Jarno</creatorcontrib><creatorcontrib>Laaksonen, Timo</creatorcontrib><creatorcontrib>Peltonen, Leena</creatorcontrib><creatorcontrib>Hirvonen, Jouni</creatorcontrib><creatorcontrib>Lehto, Vesa-Pekka</creatorcontrib><title>Cytotoxicity study of ordered mesoporous silica MCM-41 and SBA-15 microparticles on Caco-2 cells</title><title>European journal of pharmaceutics and biopharmaceutics</title><addtitle>Eur J Pharm Biopharm</addtitle><description>Cytotoxicity of ordered mesoporous silica MCM-41 and SBA-15 microparticles (fractions between 1 and 160
μm) 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
2O
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 24
h). 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 3
h incubation with threshold dose 1
mg/ml, apparently overwhelming the antioxidant defences and causing mitochondrial dysfunction, hence increasing the apoptotic signalling.</description><subject>Biocompatibility</subject><subject>Biological and medical sciences</subject><subject>Caco-2</subject><subject>Caco-2 Cells</subject><subject>Caspase 3 - metabolism</subject><subject>Caspase 7 - metabolism</subject><subject>Cell Survival - drug effects</subject><subject>Cell viability</subject><subject>Cytotoxicity</subject><subject>Drug Carriers - chemistry</subject><subject>Drug Carriers - pharmacology</subject><subject>Flow Cytometry</subject><subject>General pharmacology</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mesoporous silica</subject><subject>Microparticle</subject><subject>Microscopy, Electron, Scanning</subject><subject>Oral drug delivery</subject><subject>Particle Size</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Porosity</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Silicon Dioxide - chemistry</subject><subject>Silicon Dioxide - pharmacology</subject><subject>Surface Properties</subject><issn>0939-6411</issn><issn>1873-3441</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9v1DAQxS1ERZfCF-CAfEFwSeqxHceRuJQIaKVWHICzcfxH8iqJg51F7LfH0S5w62k00u_NvJmH0CsgNRAQ1_va7ZehpoR0NdCaEPEE7UC2rGKcw1O0Ix3rKsEBLtHznPeEEN428hm6LBLadELu0I_-uMY1_g4mrEec14M94uhxTNYlZ_HkclxiioeMcxiD0fihf6g4YD1b_PXDTQUNnoJJcdFpDWZ0GccZ99rEimLjxjG_QBdej9m9PNcr9P3Tx2_9bXX_5fNdf3NfGQ5yrSyA77yjlDVegxZMGylY05XOdEABGJdUaDYY7n3jB8KJlcMAhMqBlqPYFXp7mruk-PPg8qqmkDcHenbFvmoZY4S2khXy3aMkNIKKloiWFpSe0HJhzsl5taQw6XRUQNSWgdqrLQO1ZaCAqpJBEb0-zz8Mk7P_JH-fXoA3Z0Bno0ef9GxC_s_RRm77C_f-xLnyt1_BJZVNcLNxNiRnVmVjeMzHHy_toro</recordid><startdate>20100301</startdate><enddate>20100301</enddate><creator>Heikkilä, Teemu</creator><creator>Santos, Hélder A.</creator><creator>Kumar, Narendra</creator><creator>Murzin, Dmitry Yu</creator><creator>Salonen, Jarno</creator><creator>Laaksonen, Timo</creator><creator>Peltonen, Leena</creator><creator>Hirvonen, Jouni</creator><creator>Lehto, Vesa-Pekka</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>20100301</creationdate><title>Cytotoxicity study of ordered mesoporous silica MCM-41 and SBA-15 microparticles on Caco-2 cells</title><author>Heikkilä, Teemu ; Santos, Hélder A. ; Kumar, Narendra ; Murzin, Dmitry Yu ; Salonen, Jarno ; Laaksonen, Timo ; Peltonen, Leena ; Hirvonen, Jouni ; Lehto, Vesa-Pekka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-d11f9fe2235fa1a63ac863595fac9121134826a3bc4ff5fb040d8bb1028b27583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Biocompatibility</topic><topic>Biological and medical sciences</topic><topic>Caco-2</topic><topic>Caco-2 Cells</topic><topic>Caspase 3 - metabolism</topic><topic>Caspase 7 - metabolism</topic><topic>Cell Survival - drug effects</topic><topic>Cell viability</topic><topic>Cytotoxicity</topic><topic>Drug Carriers - chemistry</topic><topic>Drug Carriers - pharmacology</topic><topic>Flow Cytometry</topic><topic>General pharmacology</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Mesoporous silica</topic><topic>Microparticle</topic><topic>Microscopy, Electron, Scanning</topic><topic>Oral drug delivery</topic><topic>Particle Size</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Porosity</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Silicon Dioxide - chemistry</topic><topic>Silicon Dioxide - pharmacology</topic><topic>Surface Properties</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heikkilä, Teemu</creatorcontrib><creatorcontrib>Santos, Hélder A.</creatorcontrib><creatorcontrib>Kumar, Narendra</creatorcontrib><creatorcontrib>Murzin, Dmitry Yu</creatorcontrib><creatorcontrib>Salonen, Jarno</creatorcontrib><creatorcontrib>Laaksonen, Timo</creatorcontrib><creatorcontrib>Peltonen, Leena</creatorcontrib><creatorcontrib>Hirvonen, Jouni</creatorcontrib><creatorcontrib>Lehto, Vesa-Pekka</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmaceutics and biopharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heikkilä, Teemu</au><au>Santos, Hélder A.</au><au>Kumar, Narendra</au><au>Murzin, Dmitry Yu</au><au>Salonen, Jarno</au><au>Laaksonen, Timo</au><au>Peltonen, Leena</au><au>Hirvonen, Jouni</au><au>Lehto, Vesa-Pekka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxicity study of ordered mesoporous silica MCM-41 and SBA-15 microparticles on Caco-2 cells</atitle><jtitle>European journal of pharmaceutics and biopharmaceutics</jtitle><addtitle>Eur J Pharm Biopharm</addtitle><date>2010-03-01</date><risdate>2010</risdate><volume>74</volume><issue>3</issue><spage>483</spage><epage>494</epage><pages>483-494</pages><issn>0939-6411</issn><eissn>1873-3441</eissn><abstract>Cytotoxicity of ordered mesoporous silica MCM-41 and SBA-15 microparticles (fractions between 1 and 160
μm) 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
2O
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 24
h). 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 3
h incubation with threshold dose 1
mg/ml, apparently overwhelming the antioxidant defences and causing mitochondrial dysfunction, hence increasing the apoptotic signalling.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>20025968</pmid><doi>10.1016/j.ejpb.2009.12.006</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0939-6411 |
| ispartof | European journal of pharmaceutics and biopharmaceutics, 2010-03, Vol.74 (3), p.483-494 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Biocompatibility Biological and medical sciences Caco-2 Caco-2 Cells Caspase 3 - metabolism Caspase 7 - metabolism Cell Survival - drug effects Cell viability Cytotoxicity Drug Carriers - chemistry Drug Carriers - pharmacology Flow Cytometry General pharmacology Humans Medical sciences Mesoporous silica Microparticle Microscopy, Electron, Scanning Oral drug delivery Particle Size Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Porosity Reactive Oxygen Species - metabolism Silicon Dioxide - chemistry Silicon Dioxide - pharmacology Surface Properties |
| title | Cytotoxicity study of ordered mesoporous silica MCM-41 and SBA-15 microparticles on Caco-2 cells |
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