Design of Starch-graft-PEI Polymers: An Effective and Biodegradable Gene Delivery Platform
Starch and starch derivatives are widely utilized pharmaceutical excipients. The concept of this study was to make use of starch as a biodegradable backbone and to modify it with low-toxic, but poor transfecting low molecular weight polyethylenimine (PEI) in order to achieve better transfection effi...
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| Veröffentlicht in: | Biomacromolecules 2014-05, Vol.15 (5), p.1753-1761 |
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| creator | Yamada, Hiroe Loretz, Brigitta Lehr, Claus-Michael |
| description | Starch and starch derivatives are widely utilized pharmaceutical excipients. The concept of this study was to make use of starch as a biodegradable backbone and to modify it with low-toxic, but poor transfecting low molecular weight polyethylenimine (PEI) in order to achieve better transfection efficacy while maintaining enzymatic degradability. A sufficiently controllable conjugation could be achieved via a water-soluble intermediate of oxidized starch and an optimized reaction protocol. Systematic variation of MW fraction of the starch backbone and the amount of cationic side chains (0.8 kDa bPEI) yielded a series of starch-graft-PEI copolymers. Following purification and chemical characterization, nanoscale complexes with plasmid DNA were generated and studied regarding cytotoxicity and transfection efficacy. The optimal starch-graft-PEI polymers consisted of >100 kDa MW starch and contained 30% (wt) of PEI, showing similar transfection levels as 25 kDa bPEI, and being less cytotoxic and enzymatically biodegradable. |
| doi_str_mv | 10.1021/bm500128k |
| format | Article |
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The concept of this study was to make use of starch as a biodegradable backbone and to modify it with low-toxic, but poor transfecting low molecular weight polyethylenimine (PEI) in order to achieve better transfection efficacy while maintaining enzymatic degradability. A sufficiently controllable conjugation could be achieved via a water-soluble intermediate of oxidized starch and an optimized reaction protocol. Systematic variation of MW fraction of the starch backbone and the amount of cationic side chains (0.8 kDa bPEI) yielded a series of starch-graft-PEI copolymers. Following purification and chemical characterization, nanoscale complexes with plasmid DNA were generated and studied regarding cytotoxicity and transfection efficacy. The optimal starch-graft-PEI polymers consisted of >100 kDa MW starch and contained 30% (wt) of PEI, showing similar transfection levels as 25 kDa bPEI, and being less cytotoxic and enzymatically biodegradable.</description><identifier>ISSN: 1525-7797</identifier><identifier>EISSN: 1526-4602</identifier><identifier>DOI: 10.1021/bm500128k</identifier><identifier>PMID: 24684536</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Applied sciences ; Biocompatible Materials - chemical synthesis ; Biocompatible Materials - chemistry ; Biocompatible Materials - toxicity ; Biological and medical sciences ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; DNA - chemistry ; Drug Design ; Exact sciences and technology ; General pharmacology ; Humans ; Medical sciences ; Molecular Structure ; Nanostructures - chemistry ; Nanostructures - toxicity ; Natural polymers ; Particle Size ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Physicochemistry of polymers ; Plasmids - chemistry ; Polyethyleneimine - chemistry ; Polyethyleneimine - toxicity ; Solubility ; Starch - chemistry ; Starch - toxicity ; Starch and polysaccharides ; Surface Properties ; Transfection - methods</subject><ispartof>Biomacromolecules, 2014-05, Vol.15 (5), p.1753-1761</ispartof><rights>Copyright © 2014 American Chemical Society</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a378t-a938625fb56e9809116dfc3cd0775ba9af8b86f4f377c8afe5e8f356d42ae9b3</citedby><cites>FETCH-LOGICAL-a378t-a938625fb56e9809116dfc3cd0775ba9af8b86f4f377c8afe5e8f356d42ae9b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/bm500128k$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/bm500128k$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28510229$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24684536$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamada, Hiroe</creatorcontrib><creatorcontrib>Loretz, Brigitta</creatorcontrib><creatorcontrib>Lehr, Claus-Michael</creatorcontrib><title>Design of Starch-graft-PEI Polymers: An Effective and Biodegradable Gene Delivery Platform</title><title>Biomacromolecules</title><addtitle>Biomacromolecules</addtitle><description>Starch and starch derivatives are widely utilized pharmaceutical excipients. The concept of this study was to make use of starch as a biodegradable backbone and to modify it with low-toxic, but poor transfecting low molecular weight polyethylenimine (PEI) in order to achieve better transfection efficacy while maintaining enzymatic degradability. A sufficiently controllable conjugation could be achieved via a water-soluble intermediate of oxidized starch and an optimized reaction protocol. Systematic variation of MW fraction of the starch backbone and the amount of cationic side chains (0.8 kDa bPEI) yielded a series of starch-graft-PEI copolymers. Following purification and chemical characterization, nanoscale complexes with plasmid DNA were generated and studied regarding cytotoxicity and transfection efficacy. The optimal starch-graft-PEI polymers consisted of >100 kDa MW starch and contained 30% (wt) of PEI, showing similar transfection levels as 25 kDa bPEI, and being less cytotoxic and enzymatically biodegradable.</description><subject>Applied sciences</subject><subject>Biocompatible Materials - chemical synthesis</subject><subject>Biocompatible Materials - chemistry</subject><subject>Biocompatible Materials - toxicity</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>DNA - chemistry</subject><subject>Drug Design</subject><subject>Exact sciences and technology</subject><subject>General pharmacology</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Molecular Structure</subject><subject>Nanostructures - chemistry</subject><subject>Nanostructures - toxicity</subject><subject>Natural polymers</subject><subject>Particle Size</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Physicochemistry of polymers</subject><subject>Plasmids - chemistry</subject><subject>Polyethyleneimine - chemistry</subject><subject>Polyethyleneimine - toxicity</subject><subject>Solubility</subject><subject>Starch - chemistry</subject><subject>Starch - toxicity</subject><subject>Starch and polysaccharides</subject><subject>Surface Properties</subject><subject>Transfection - methods</subject><issn>1525-7797</issn><issn>1526-4602</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0E1LAzEQBuAgitbqwT8guQh6WE02m2zirbb1AwoW9ORlmc1OdHU_arIV-u9dbdWLpxmYh3fgJeSIs3POYn6R15IxHuu3LTLgMlZRoli8_b3LKE1Nukf2Q3hljBmRyF2yFydKJ1KoAXmaYCifG9o6-tCBty_RswfXRfPpHZ231apGHy7pqKFT59B25QdSaAp6VbYF9rKAvEJ6gw3SCVb91a_ovILOtb4-IDsOqoCHmzkkj9fTx_FtNLu_uRuPZhGIVHcRGKFVLF0uFRrNDOeqcFbYgqWpzMGA07lWLnEiTa0GhxK1E1IVSQxocjEkp-vYhW_flxi6rC6DxaqCBttlyLgUiU4016anZ2tqfRuCR5ctfFmDX2WcZV9NZr9N9vZ4E7vMayx-5U91PTjZAAgWKuehsWX4c1r2ibH5c2BD9toufdOX8c_DT7mshk8</recordid><startdate>20140512</startdate><enddate>20140512</enddate><creator>Yamada, Hiroe</creator><creator>Loretz, Brigitta</creator><creator>Lehr, Claus-Michael</creator><general>American Chemical Society</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>7QO</scope><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20140512</creationdate><title>Design of Starch-graft-PEI Polymers: An Effective and Biodegradable Gene Delivery Platform</title><author>Yamada, Hiroe ; Loretz, Brigitta ; Lehr, Claus-Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a378t-a938625fb56e9809116dfc3cd0775ba9af8b86f4f377c8afe5e8f356d42ae9b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Applied sciences</topic><topic>Biocompatible Materials - chemical synthesis</topic><topic>Biocompatible Materials - chemistry</topic><topic>Biocompatible Materials - toxicity</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>DNA - chemistry</topic><topic>Drug Design</topic><topic>Exact sciences and technology</topic><topic>General pharmacology</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Molecular Structure</topic><topic>Nanostructures - chemistry</topic><topic>Nanostructures - toxicity</topic><topic>Natural polymers</topic><topic>Particle Size</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Physicochemistry of polymers</topic><topic>Plasmids - chemistry</topic><topic>Polyethyleneimine - chemistry</topic><topic>Polyethyleneimine - toxicity</topic><topic>Solubility</topic><topic>Starch - chemistry</topic><topic>Starch - toxicity</topic><topic>Starch and polysaccharides</topic><topic>Surface Properties</topic><topic>Transfection - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamada, Hiroe</creatorcontrib><creatorcontrib>Loretz, Brigitta</creatorcontrib><creatorcontrib>Lehr, Claus-Michael</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>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Biomacromolecules</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamada, Hiroe</au><au>Loretz, Brigitta</au><au>Lehr, Claus-Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design of Starch-graft-PEI Polymers: An Effective and Biodegradable Gene Delivery Platform</atitle><jtitle>Biomacromolecules</jtitle><addtitle>Biomacromolecules</addtitle><date>2014-05-12</date><risdate>2014</risdate><volume>15</volume><issue>5</issue><spage>1753</spage><epage>1761</epage><pages>1753-1761</pages><issn>1525-7797</issn><eissn>1526-4602</eissn><abstract>Starch and starch derivatives are widely utilized pharmaceutical excipients. The concept of this study was to make use of starch as a biodegradable backbone and to modify it with low-toxic, but poor transfecting low molecular weight polyethylenimine (PEI) in order to achieve better transfection efficacy while maintaining enzymatic degradability. A sufficiently controllable conjugation could be achieved via a water-soluble intermediate of oxidized starch and an optimized reaction protocol. Systematic variation of MW fraction of the starch backbone and the amount of cationic side chains (0.8 kDa bPEI) yielded a series of starch-graft-PEI copolymers. Following purification and chemical characterization, nanoscale complexes with plasmid DNA were generated and studied regarding cytotoxicity and transfection efficacy. 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| subjects | Applied sciences Biocompatible Materials - chemical synthesis Biocompatible Materials - chemistry Biocompatible Materials - toxicity Biological and medical sciences Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects DNA - chemistry Drug Design Exact sciences and technology General pharmacology Humans Medical sciences Molecular Structure Nanostructures - chemistry Nanostructures - toxicity Natural polymers Particle Size Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Physicochemistry of polymers Plasmids - chemistry Polyethyleneimine - chemistry Polyethyleneimine - toxicity Solubility Starch - chemistry Starch - toxicity Starch and polysaccharides Surface Properties Transfection - methods |
| title | Design of Starch-graft-PEI Polymers: An Effective and Biodegradable Gene Delivery Platform |
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