Transport of dendrimer nanocarriers through epithelial cells via the transcellular route
The mechanism of transport of G3 PAMAM and surface-modified (with lauroyl chains) G3 PAMAM dendrimer nanocarriers across Caco-2 cell monolayers has been investigated. Flow-cytometry studies following quenching of extracellular fluorescence demonstrated the cellular internalisation of dendrimers. Opt...
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| Veröffentlicht in: | Journal of controlled release 2004-06, Vol.97 (2), p.259-267 |
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| creator | Jevprasesphant, Rachaneekorn Penny, Jeffrey Attwood, David D'Emanuele, Antony |
| description | The mechanism of transport of G3 PAMAM and surface-modified (with lauroyl chains) G3 PAMAM dendrimer nanocarriers across Caco-2 cell monolayers has been investigated. Flow-cytometry studies following quenching of extracellular fluorescence demonstrated the cellular internalisation of dendrimers. Optical sectioning of cells incubated with fluorescein isothiocyanate (FITC)-conjugated dendrimer and lauroyl–dendrimer using confocal laser scanning microscopy revealed colocalisation of a marker for cell nuclei (4′,6-diamidino-2-phenylindole, DAPI) and FITC fluorescence, also suggesting cellular internalisation of dendrimers. Transmission electron microscopic analyses of cells incubated with gold-labelled G3 PAMAM dendrimers confirmed endocytosis-mediated cellular internalisation when dendrimers were applied to the apical domain of Caco-2 cells. These findings are in agreement with our previous studies using Caco-2 cell monolayers that showed a significant decrease of dendrimer uptake in the presence of colchicine (endocytosis inhibitor) and when temperature was reduced from 37 to 4 °C. |
| doi_str_mv | 10.1016/j.jconrel.2004.03.022 |
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Flow-cytometry studies following quenching of extracellular fluorescence demonstrated the cellular internalisation of dendrimers. Optical sectioning of cells incubated with fluorescein isothiocyanate (FITC)-conjugated dendrimer and lauroyl–dendrimer using confocal laser scanning microscopy revealed colocalisation of a marker for cell nuclei (4′,6-diamidino-2-phenylindole, DAPI) and FITC fluorescence, also suggesting cellular internalisation of dendrimers. Transmission electron microscopic analyses of cells incubated with gold-labelled G3 PAMAM dendrimers confirmed endocytosis-mediated cellular internalisation when dendrimers were applied to the apical domain of Caco-2 cells. These findings are in agreement with our previous studies using Caco-2 cell monolayers that showed a significant decrease of dendrimer uptake in the presence of colchicine (endocytosis inhibitor) and when temperature was reduced from 37 to 4 °C.</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2004.03.022</identifier><identifier>PMID: 15196753</identifier><identifier>CODEN: JCREEC</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Biological and medical sciences ; Biological Transport ; Caco-2 Cells ; Dendrimers ; Drug Carriers - pharmacokinetics ; Drug delivery ; Endocytosis ; Epithelial Cells - metabolism ; Flow Cytometry ; Fluorescein-5-isothiocyanate ; Fluorescent Dyes ; General pharmacology ; Humans ; Mechanism of transepithelial transport of dendrimer nanocarriers ; Medical sciences ; Microscopy, Confocal ; Microscopy, Electron, Transmission ; Nanostructures ; Permeability ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Polyamines - pharmacokinetics ; Transcellular and paracellular routes ; Trypan Blue</subject><ispartof>Journal of controlled release, 2004-06, Vol.97 (2), p.259-267</ispartof><rights>2004 Elsevier B.V.</rights><rights>2004 INIST-CNRS</rights><rights>Copyright 2004 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c457t-d721db07f95f6445f1e59d1b87f0c87333c34760c28ddb7408220e79ccdf61b73</citedby><cites>FETCH-LOGICAL-c457t-d721db07f95f6445f1e59d1b87f0c87333c34760c28ddb7408220e79ccdf61b73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jconrel.2004.03.022$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15854473$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15196753$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jevprasesphant, Rachaneekorn</creatorcontrib><creatorcontrib>Penny, Jeffrey</creatorcontrib><creatorcontrib>Attwood, David</creatorcontrib><creatorcontrib>D'Emanuele, Antony</creatorcontrib><title>Transport of dendrimer nanocarriers through epithelial cells via the transcellular route</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>The mechanism of transport of G3 PAMAM and surface-modified (with lauroyl chains) G3 PAMAM dendrimer nanocarriers across Caco-2 cell monolayers has been investigated. Flow-cytometry studies following quenching of extracellular fluorescence demonstrated the cellular internalisation of dendrimers. Optical sectioning of cells incubated with fluorescein isothiocyanate (FITC)-conjugated dendrimer and lauroyl–dendrimer using confocal laser scanning microscopy revealed colocalisation of a marker for cell nuclei (4′,6-diamidino-2-phenylindole, DAPI) and FITC fluorescence, also suggesting cellular internalisation of dendrimers. Transmission electron microscopic analyses of cells incubated with gold-labelled G3 PAMAM dendrimers confirmed endocytosis-mediated cellular internalisation when dendrimers were applied to the apical domain of Caco-2 cells. These findings are in agreement with our previous studies using Caco-2 cell monolayers that showed a significant decrease of dendrimer uptake in the presence of colchicine (endocytosis inhibitor) and when temperature was reduced from 37 to 4 °C.</description><subject>Biological and medical sciences</subject><subject>Biological Transport</subject><subject>Caco-2 Cells</subject><subject>Dendrimers</subject><subject>Drug Carriers - pharmacokinetics</subject><subject>Drug delivery</subject><subject>Endocytosis</subject><subject>Epithelial Cells - metabolism</subject><subject>Flow Cytometry</subject><subject>Fluorescein-5-isothiocyanate</subject><subject>Fluorescent Dyes</subject><subject>General pharmacology</subject><subject>Humans</subject><subject>Mechanism of transepithelial transport of dendrimer nanocarriers</subject><subject>Medical sciences</subject><subject>Microscopy, Confocal</subject><subject>Microscopy, Electron, Transmission</subject><subject>Nanostructures</subject><subject>Permeability</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Polyamines - pharmacokinetics</subject><subject>Transcellular and paracellular routes</subject><subject>Trypan Blue</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1r3DAQhkVpaTZJf0KKLs3Nrj4t-xRKaD4gkEsKuQlZGmW1eK2tZAf67yt3DektpwHNM6N3HoQuKKkpoc33Xb2zcUww1IwQURNeE8Y-oA1tFa9E18mPaFO4tuKN7E7Qac47QojkQn1GJ1TSrlGSb9DzUzJjPsQ04eixg9GlsIeERzNGa1IKkDKetinOL1sMhzBtYQhmwBaGIePXYEoT8LQsWZ7mwSRc4AnO0Sdvhgxf1nqGft38fLq-qx4eb--vfzxUVkg1VU4x6nqifCd9I4T0FGTnaN8qT2w5hXNbIjfEsta5XgnSMkZAddY639Be8TN0edx7SPH3DHnS-_AvihkhzlkrRhinoimgPII2xZwTeH0op5r0R1OiF6V6p1elelGqCddFaZn7un4w93twb1OrwwJ8WwGTrRl8cWFD_o9rpRBq4a6OHBQdr0WszjbAaMGFBHbSLoZ3ovwFN8mYkw</recordid><startdate>20040618</startdate><enddate>20040618</enddate><creator>Jevprasesphant, Rachaneekorn</creator><creator>Penny, Jeffrey</creator><creator>Attwood, David</creator><creator>D'Emanuele, Antony</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>7X8</scope></search><sort><creationdate>20040618</creationdate><title>Transport of dendrimer nanocarriers through epithelial cells via the transcellular route</title><author>Jevprasesphant, Rachaneekorn ; Penny, Jeffrey ; Attwood, David ; D'Emanuele, Antony</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c457t-d721db07f95f6445f1e59d1b87f0c87333c34760c28ddb7408220e79ccdf61b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Biological and medical sciences</topic><topic>Biological Transport</topic><topic>Caco-2 Cells</topic><topic>Dendrimers</topic><topic>Drug Carriers - pharmacokinetics</topic><topic>Drug delivery</topic><topic>Endocytosis</topic><topic>Epithelial Cells - metabolism</topic><topic>Flow Cytometry</topic><topic>Fluorescein-5-isothiocyanate</topic><topic>Fluorescent Dyes</topic><topic>General pharmacology</topic><topic>Humans</topic><topic>Mechanism of transepithelial transport of dendrimer nanocarriers</topic><topic>Medical sciences</topic><topic>Microscopy, Confocal</topic><topic>Microscopy, Electron, Transmission</topic><topic>Nanostructures</topic><topic>Permeability</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Polyamines - pharmacokinetics</topic><topic>Transcellular and paracellular routes</topic><topic>Trypan Blue</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jevprasesphant, Rachaneekorn</creatorcontrib><creatorcontrib>Penny, Jeffrey</creatorcontrib><creatorcontrib>Attwood, David</creatorcontrib><creatorcontrib>D'Emanuele, Antony</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>MEDLINE - Academic</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jevprasesphant, Rachaneekorn</au><au>Penny, Jeffrey</au><au>Attwood, David</au><au>D'Emanuele, Antony</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transport of dendrimer nanocarriers through epithelial cells via the transcellular route</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2004-06-18</date><risdate>2004</risdate><volume>97</volume><issue>2</issue><spage>259</spage><epage>267</epage><pages>259-267</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><coden>JCREEC</coden><abstract>The mechanism of transport of G3 PAMAM and surface-modified (with lauroyl chains) G3 PAMAM dendrimer nanocarriers across Caco-2 cell monolayers has been investigated. Flow-cytometry studies following quenching of extracellular fluorescence demonstrated the cellular internalisation of dendrimers. Optical sectioning of cells incubated with fluorescein isothiocyanate (FITC)-conjugated dendrimer and lauroyl–dendrimer using confocal laser scanning microscopy revealed colocalisation of a marker for cell nuclei (4′,6-diamidino-2-phenylindole, DAPI) and FITC fluorescence, also suggesting cellular internalisation of dendrimers. Transmission electron microscopic analyses of cells incubated with gold-labelled G3 PAMAM dendrimers confirmed endocytosis-mediated cellular internalisation when dendrimers were applied to the apical domain of Caco-2 cells. These findings are in agreement with our previous studies using Caco-2 cell monolayers that showed a significant decrease of dendrimer uptake in the presence of colchicine (endocytosis inhibitor) and when temperature was reduced from 37 to 4 °C.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>15196753</pmid><doi>10.1016/j.jconrel.2004.03.022</doi><tpages>9</tpages></addata></record> |
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| subjects | Biological and medical sciences Biological Transport Caco-2 Cells Dendrimers Drug Carriers - pharmacokinetics Drug delivery Endocytosis Epithelial Cells - metabolism Flow Cytometry Fluorescein-5-isothiocyanate Fluorescent Dyes General pharmacology Humans Mechanism of transepithelial transport of dendrimer nanocarriers Medical sciences Microscopy, Confocal Microscopy, Electron, Transmission Nanostructures Permeability Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Polyamines - pharmacokinetics Transcellular and paracellular routes Trypan Blue |
| title | Transport of dendrimer nanocarriers through epithelial cells via the transcellular route |
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