Pyrrolidone-modified PAMAM dendrimers enhance anti-inflammatory potential of indomethacin in vitro
[Display omitted] •4-carbomethoxypyrrolidone-coated PAMAM dendrimers as carriers for indomethacin.•Dendrimers do not hinder the inhibitory effect of the drug on cyclooxygenases.•Drug-dendrimer complexes exhibit improved anti-inflammatory activity in vitro. The therapeutic effect of indomethacin, a w...
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| Veröffentlicht in: | Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2019-09, Vol.181, p.959-962 |
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| container_title | Colloids and surfaces, B, Biointerfaces |
| container_volume | 181 |
| creator | Gorzkiewicz, Michał Janaszewska, Anna Ficker, Mario Svenningsen, Søren W. Christensen, Jørn B. Klajnert-Maculewicz, Barbara |
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•4-carbomethoxypyrrolidone-coated PAMAM dendrimers as carriers for indomethacin.•Dendrimers do not hinder the inhibitory effect of the drug on cyclooxygenases.•Drug-dendrimer complexes exhibit improved anti-inflammatory activity in vitro.
The therapeutic effect of indomethacin, a water-insoluble non-steroidal anti-inflammatory drug, requires its efficient transport through cellular membranes and accumulation inside the target cells. The application of dendritic polymers has been proposed for the improvement of the drug’s solubility and intracellular delivery. In this study we evaluated the anti-inflammatory potential of novel, highly-biocompatible 4-carbomethoxypyrrolidone-coated PAMAM dendrimers loaded with indomethacin. Our results indicate that complexation with dendrimers do not hamper the inhibitory action of indomethacin towards cyclooxygenases. Drug-dendrimer formulations exhibited improved anti-inflammatory activity in in vitro-cultured cellular models, showing enhanced inhibition of prostaglandin secretion and significantly decreased expression of NF-κB marker genes compared to free drug. |
| doi_str_mv | 10.1016/j.colsurfb.2019.06.056 |
| format | Article |
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•4-carbomethoxypyrrolidone-coated PAMAM dendrimers as carriers for indomethacin.•Dendrimers do not hinder the inhibitory effect of the drug on cyclooxygenases.•Drug-dendrimer complexes exhibit improved anti-inflammatory activity in vitro.
The therapeutic effect of indomethacin, a water-insoluble non-steroidal anti-inflammatory drug, requires its efficient transport through cellular membranes and accumulation inside the target cells. The application of dendritic polymers has been proposed for the improvement of the drug’s solubility and intracellular delivery. In this study we evaluated the anti-inflammatory potential of novel, highly-biocompatible 4-carbomethoxypyrrolidone-coated PAMAM dendrimers loaded with indomethacin. Our results indicate that complexation with dendrimers do not hamper the inhibitory action of indomethacin towards cyclooxygenases. Drug-dendrimer formulations exhibited improved anti-inflammatory activity in in vitro-cultured cellular models, showing enhanced inhibition of prostaglandin secretion and significantly decreased expression of NF-κB marker genes compared to free drug.</description><identifier>ISSN: 0927-7765</identifier><identifier>EISSN: 1873-4367</identifier><identifier>DOI: 10.1016/j.colsurfb.2019.06.056</identifier><identifier>PMID: 31382346</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Anti-Inflammatory Agents, Non-Steroidal - chemistry ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; COX ; Dendrimers - chemistry ; Humans ; Indomethacin ; Indomethacin - chemistry ; Indomethacin - pharmacology ; NF-kappa B - metabolism ; NF-κB ; PAMAM dendrimer ; Prostaglandin ; Prostaglandins - metabolism ; Pyrrolidinones - chemistry ; Pyrrolidone ; U937 Cells</subject><ispartof>Colloids and surfaces, B, Biointerfaces, 2019-09, Vol.181, p.959-962</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-e8ab27755e2018e8584f0b854fa9badfb390e4802041f9f1702f47980d24ec8c3</citedby><cites>FETCH-LOGICAL-c405t-e8ab27755e2018e8584f0b854fa9badfb390e4802041f9f1702f47980d24ec8c3</cites><orcidid>0000-0001-9258-3626 ; 0000-0003-3459-8947</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.colsurfb.2019.06.056$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31382346$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gorzkiewicz, Michał</creatorcontrib><creatorcontrib>Janaszewska, Anna</creatorcontrib><creatorcontrib>Ficker, Mario</creatorcontrib><creatorcontrib>Svenningsen, Søren W.</creatorcontrib><creatorcontrib>Christensen, Jørn B.</creatorcontrib><creatorcontrib>Klajnert-Maculewicz, Barbara</creatorcontrib><title>Pyrrolidone-modified PAMAM dendrimers enhance anti-inflammatory potential of indomethacin in vitro</title><title>Colloids and surfaces, B, Biointerfaces</title><addtitle>Colloids Surf B Biointerfaces</addtitle><description>[Display omitted]
•4-carbomethoxypyrrolidone-coated PAMAM dendrimers as carriers for indomethacin.•Dendrimers do not hinder the inhibitory effect of the drug on cyclooxygenases.•Drug-dendrimer complexes exhibit improved anti-inflammatory activity in vitro.
The therapeutic effect of indomethacin, a water-insoluble non-steroidal anti-inflammatory drug, requires its efficient transport through cellular membranes and accumulation inside the target cells. The application of dendritic polymers has been proposed for the improvement of the drug’s solubility and intracellular delivery. In this study we evaluated the anti-inflammatory potential of novel, highly-biocompatible 4-carbomethoxypyrrolidone-coated PAMAM dendrimers loaded with indomethacin. Our results indicate that complexation with dendrimers do not hamper the inhibitory action of indomethacin towards cyclooxygenases. Drug-dendrimer formulations exhibited improved anti-inflammatory activity in in vitro-cultured cellular models, showing enhanced inhibition of prostaglandin secretion and significantly decreased expression of NF-κB marker genes compared to free drug.</description><subject>Anti-Inflammatory Agents, Non-Steroidal - chemistry</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>COX</subject><subject>Dendrimers - chemistry</subject><subject>Humans</subject><subject>Indomethacin</subject><subject>Indomethacin - chemistry</subject><subject>Indomethacin - pharmacology</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB</subject><subject>PAMAM dendrimer</subject><subject>Prostaglandin</subject><subject>Prostaglandins - metabolism</subject><subject>Pyrrolidinones - chemistry</subject><subject>Pyrrolidone</subject><subject>U937 Cells</subject><issn>0927-7765</issn><issn>1873-4367</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE9P3DAQxS3UChbKV0A59pIwdhzbuXWF-k8ClUN7thx7LLxK7MXOIu23r9FCrz2NZvTePL0fITcUOgpU3O46m-ZyyH7qGNCxA9HBIM7IhirZt7wX8gPZwMhkK6UYLshlKTsAYJzKc3LR016xnosNmR6POac5uBSxXZILPqBrHrcP24fGYXQ5LJhLg_HJRIuNiWtoQ_SzWRazpnxs9mnFejRzk3wToksLrk_GhliX5iWsOX0iH72ZC16_zSvy59vX33c_2vtf33_ebe9by2FYW1RmYlIOA9ZCCtWguIdJDdybcTLOT_0IyBUw4NSPnkpgnstRgWMcrbL9Ffl8-rvP6fmAZdVLKBbn2URMh6IZE2qsZKioUnGS2pxKyej1vhY1-agp6Fe-eqff-epXvhqErnyr8eYt4zAt6P7Z3oFWwZeTAGvTl4BZFxuwonMho121S-F_GX8BGiuQ5A</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Gorzkiewicz, Michał</creator><creator>Janaszewska, Anna</creator><creator>Ficker, Mario</creator><creator>Svenningsen, Søren W.</creator><creator>Christensen, Jørn B.</creator><creator>Klajnert-Maculewicz, Barbara</creator><general>Elsevier B.V</general><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><orcidid>https://orcid.org/0000-0001-9258-3626</orcidid><orcidid>https://orcid.org/0000-0003-3459-8947</orcidid></search><sort><creationdate>20190901</creationdate><title>Pyrrolidone-modified PAMAM dendrimers enhance anti-inflammatory potential of indomethacin in vitro</title><author>Gorzkiewicz, Michał ; Janaszewska, Anna ; Ficker, Mario ; Svenningsen, Søren W. ; Christensen, Jørn B. ; Klajnert-Maculewicz, Barbara</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c405t-e8ab27755e2018e8584f0b854fa9badfb390e4802041f9f1702f47980d24ec8c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Anti-Inflammatory Agents, Non-Steroidal - chemistry</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>COX</topic><topic>Dendrimers - chemistry</topic><topic>Humans</topic><topic>Indomethacin</topic><topic>Indomethacin - chemistry</topic><topic>Indomethacin - pharmacology</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB</topic><topic>PAMAM dendrimer</topic><topic>Prostaglandin</topic><topic>Prostaglandins - metabolism</topic><topic>Pyrrolidinones - chemistry</topic><topic>Pyrrolidone</topic><topic>U937 Cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gorzkiewicz, Michał</creatorcontrib><creatorcontrib>Janaszewska, Anna</creatorcontrib><creatorcontrib>Ficker, Mario</creatorcontrib><creatorcontrib>Svenningsen, Søren W.</creatorcontrib><creatorcontrib>Christensen, Jørn B.</creatorcontrib><creatorcontrib>Klajnert-Maculewicz, Barbara</creatorcontrib><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>Colloids and surfaces, B, Biointerfaces</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gorzkiewicz, Michał</au><au>Janaszewska, Anna</au><au>Ficker, Mario</au><au>Svenningsen, Søren W.</au><au>Christensen, Jørn B.</au><au>Klajnert-Maculewicz, Barbara</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pyrrolidone-modified PAMAM dendrimers enhance anti-inflammatory potential of indomethacin in vitro</atitle><jtitle>Colloids and surfaces, B, Biointerfaces</jtitle><addtitle>Colloids Surf B Biointerfaces</addtitle><date>2019-09-01</date><risdate>2019</risdate><volume>181</volume><spage>959</spage><epage>962</epage><pages>959-962</pages><issn>0927-7765</issn><eissn>1873-4367</eissn><abstract>[Display omitted]
•4-carbomethoxypyrrolidone-coated PAMAM dendrimers as carriers for indomethacin.•Dendrimers do not hinder the inhibitory effect of the drug on cyclooxygenases.•Drug-dendrimer complexes exhibit improved anti-inflammatory activity in vitro.
The therapeutic effect of indomethacin, a water-insoluble non-steroidal anti-inflammatory drug, requires its efficient transport through cellular membranes and accumulation inside the target cells. The application of dendritic polymers has been proposed for the improvement of the drug’s solubility and intracellular delivery. In this study we evaluated the anti-inflammatory potential of novel, highly-biocompatible 4-carbomethoxypyrrolidone-coated PAMAM dendrimers loaded with indomethacin. Our results indicate that complexation with dendrimers do not hamper the inhibitory action of indomethacin towards cyclooxygenases. Drug-dendrimer formulations exhibited improved anti-inflammatory activity in in vitro-cultured cellular models, showing enhanced inhibition of prostaglandin secretion and significantly decreased expression of NF-κB marker genes compared to free drug.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>31382346</pmid><doi>10.1016/j.colsurfb.2019.06.056</doi><tpages>4</tpages><orcidid>https://orcid.org/0000-0001-9258-3626</orcidid><orcidid>https://orcid.org/0000-0003-3459-8947</orcidid></addata></record> |
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| subjects | Anti-Inflammatory Agents, Non-Steroidal - chemistry Anti-Inflammatory Agents, Non-Steroidal - pharmacology COX Dendrimers - chemistry Humans Indomethacin Indomethacin - chemistry Indomethacin - pharmacology NF-kappa B - metabolism NF-κB PAMAM dendrimer Prostaglandin Prostaglandins - metabolism Pyrrolidinones - chemistry Pyrrolidone U937 Cells |
| title | Pyrrolidone-modified PAMAM dendrimers enhance anti-inflammatory potential of indomethacin in vitro |
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