| Inulin is a promising cryo- and lyoprotectant for PEGylated lipoplexes. | |
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MedLine Citation:
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PMID: 15763627 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The aim of this study was to investigate whether the oligosaccharides dextran and inulin are able to prevent aggregation of lipoplexes based on 1,2-dioleoyl-3-trimethylammonium-propane and dioleoylphosphatidyl-ethanolamine with and without distearoylphosphatidylethanolamine-polyethyleneglycol (PEGylated and nonPEGylated lipoplexes, respectively) during storage. The lipoplexes, dispersed in the oligosaccharide solution were frozen and subsequently stored at subzero temperature or freeze dried and subsequently stored at 37 degrees C. When lipoplexes in frozen dispersions were stored below the glass transition temperature of the maximally freeze concentrated fraction (Tg') of the oligosaccharide solutions severe aggregation of the nonPEGylated lipoplexes was prevented for 3 months by both inulin and dextran. However, while dextran failed to stabilize the frozen PEGylated lipoplexes (as in most cases full aggregation occurred in short time) inulin successfully protected them against aggregation. Compared to dextran, inulin was also a superior lyoprotectant of PEGylated lipoplexes: during freeze drying and subsequent storage at 37 degrees C of the dried powders for 3 months the PEGylated lipoplexes maintained their original size when dispersed in inulin matrices while in dextran matrices they fully aggregated in most cases. It is hypothesized that the aggregation of the PEGylated lipoplexes in dextran solutions is caused by the well known incompatibility between dextrans and PEG. This is further supported by the observation that inulins and PEG are compatible. It is concluded that oligosaccharides can prevent severe aggregation of nonPEGylated lipoplexes. The same holds for PEGylated lipoplexes provided that the oligosaccharide is compatible with PEG. Finally, this work also shows that the higher Tg' of oligosaccharides makes them more versatile cryoprotectants than disaccharides like sucrose or trehalose as the frozen dispersions can be stored at higher temperatures for prolonged periods of time. Furthermore, it is proposed that oligosaccharides are also more versatile lyoprotectants than the disaccharides because they can be exposed to higher relative humidities without passing the glass transition temperature. |
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Authors:
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W L J Hinrichs; N N Sanders; S C De Smedt; J Demeester; H W Frijlink |
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Publication Detail:
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Type: Journal Article Date: 2005-01-15 |
Journal Detail:
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Title: Journal of controlled release : official journal of the Controlled Release Society Volume: 103 ISSN: 0168-3659 ISO Abbreviation: J Control Release Publication Date: 2005 Mar |
Date Detail:
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Created Date: 2005-03-14 Completed Date: 2005-08-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8607908 Medline TA: J Control Release Country: Netherlands |
Other Details:
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Languages: eng Pagination: 465-79 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. W.L.J.Hinrichs@farm.rug.nl |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Drug Stability Drug Storage Freeze Drying Inulin / chemistry* Liposomes Oligonucleotides, Antisense / administration & dosage*, chemistry Particle Size Polyethylene Glycols / chemistry* Temperature |
| Chemical | |
Reg. No./Substance:
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0/Liposomes; 0/Oligonucleotides, Antisense; 0/Polyethylene Glycols; 9005-80-5/Inulin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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