| An acid sensitive ketal-based polyethylene glycol-oligoethylenimine copolymer mediates improved transfection efficiency at reduced toxicity. | |
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MedLine Citation:
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PMID: 18751876 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Dynamic PEG-polycation copolymers that release PEG and degrade into small fragments after cell entry might present efficient and biocompatible gene carriers. METHODS: PEG-OEI-MK was synthesized by copolymerization of 5 kDa polyethyleneglycol (PEG) and 800 Da oligoethylenimines through acid-degradable acetone-bis-(N-maleimidoethyl)ketal linkers (MK). To evaluate any benefit of the reversible over stable linkage, also the corresponding pH-stable analog, PEG-OEI-BM, was synthesized via ether linkages. Luciferase and GFP expression plasmids were used for transfections, in vivo biocompatibility was evaluated by intravenous application of polymers in Balb/c mice. RESULTS: PEG-OEI-MK showed efficient DNA binding as analyzed by ethidium bromide exclusion, resulting in formation of polyplexes with sizes around 100 nm and surface charges of below 5 mV zeta potential. This surface shielding of PEG-OEI-MK polyplexes remained stable at neutral pH 7.4, while polyplexes deshielded and aggregated at pH 5 within 15-30 min. Cell culture experiments demonstrated reduced polymer toxicity compared to the non-PEGylated OEI-MK. Transfection experiments demonstrated reduced gene expression of PEG-OEI-BM compared with the non-PEGylated analog OEI-BM, whereas the pH-reversible polymer PEG-OEI-MK mediated a significant increased transfection efficiency over the non-PEGylated OEI-MK. CONCLUSIONS: PEG-OEI-MK mediated the highest gene transfer at lowest cytotoxicity levels and also best in vivo biocompatibility. |
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Authors:
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Veronika Knorr; Manfred Ogris; Ernst Wagner |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-08-27 |
Journal Detail:
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Title: Pharmaceutical research Volume: 25 ISSN: 0724-8741 ISO Abbreviation: Pharm. Res. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-12-02 Completed Date: 2009-02-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: United States |
Other Details:
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Languages: eng Pagination: 2937-45 Citation Subset: IM |
Affiliation:
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Pharmaceutical Biology-Biotechnology, Center for Drug Research and Center for NanoScience, Ludwig-Maximilians-Universität München, Munich, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biocompatible Materials / chemistry Female Hydrogen-Ion Concentration Mice Mice, Inbred BALB C Polyethylene Glycols / chemistry Polyethyleneimine / chemistry Polymers / chemical synthesis, chemistry*, toxicity Transfection / methods* |
| Chemical | |
Reg. No./Substance:
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0/Biocompatible Materials; 0/Polyethylene Glycols; 0/Polymers; 9002-98-6/Polyethyleneimine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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