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Relationship between the physical shape and the efficiency of oligomeric chitosan as a gene delivery system in vitro and in vivo.

Identifieur interne : 002474 ( PubMed/Corpus ); précédent : 002473; suivant : 002475

Relationship between the physical shape and the efficiency of oligomeric chitosan as a gene delivery system in vitro and in vivo.

Auteurs : M. Köping-Högg Rd ; Y S Mel'Nikova ; K M V Rum ; B. Lindman ; P. Artursson

Source :

RBID : pubmed:12539151

English descriptors

Abstract

Chitosans of high molecular weights have emerged as efficient nonviral gene delivery systems, but the properties and efficiency of well-defined low molecular weight chitosans (<5 kDa) have not been studied. We therefore characterized DNA complexes of such low molecular weight chitosans and related their physical shape and stability to their efficiency as gene delivery systems in vitro and in vivo.

DOI: 10.1002/jgm.327
PubMed: 12539151

Links to Exploration step

pubmed:12539151

Le document en format XML

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<title xml:lang="en">Relationship between the physical shape and the efficiency of oligomeric chitosan as a gene delivery system in vitro and in vivo.</title>
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<name sortKey="Koping Hogg Rd, M" sort="Koping Hogg Rd, M" uniqKey="Koping Hogg Rd M" first="M" last="Köping-Högg Rd">M. Köping-Högg Rd</name>
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<nlm:affiliation>Department of Pharmacy, Uppsala University, Uppsala, Sweden.</nlm:affiliation>
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<name sortKey="Mel Nikova, Y S" sort="Mel Nikova, Y S" uniqKey="Mel Nikova Y" first="Y S" last="Mel'Nikova">Y S Mel'Nikova</name>
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<name sortKey="V Rum, K M" sort="V Rum, K M" uniqKey="V Rum K" first="K M" last="V Rum">K M V Rum</name>
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<name sortKey="Lindman, B" sort="Lindman, B" uniqKey="Lindman B" first="B" last="Lindman">B. Lindman</name>
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<name sortKey="Artursson, P" sort="Artursson, P" uniqKey="Artursson P" first="P" last="Artursson">P. Artursson</name>
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<term>Adjuvants, Pharmaceutic (chemistry)</term>
<term>Adjuvants, Pharmaceutic (metabolism)</term>
<term>Animals</term>
<term>Cell Line</term>
<term>Chitin (analogs & derivatives)</term>
<term>Chitin (chemistry)</term>
<term>Chitin (metabolism)</term>
<term>Chitosan</term>
<term>DNA (chemistry)</term>
<term>DNA (metabolism)</term>
<term>Gene Expression</term>
<term>Gene Transfer Techniques</term>
<term>Genes, Reporter</term>
<term>Humans</term>
<term>Hydrogen-Ion Concentration</term>
<term>Macromolecular Substances</term>
<term>Mice</term>
<term>Molecular Weight</term>
<term>Nucleic Acid Conformation</term>
<term>Polymers (chemistry)</term>
<term>Polymers (metabolism)</term>
<term>Sodium Chloride (chemistry)</term>
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<term>Chitin</term>
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<term>Adjuvants, Pharmaceutic</term>
<term>Chitin</term>
<term>DNA</term>
<term>Polymers</term>
<term>Sodium Chloride</term>
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<term>Polymers</term>
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<term>Animals</term>
<term>Cell Line</term>
<term>Chitosan</term>
<term>Gene Expression</term>
<term>Gene Transfer Techniques</term>
<term>Genes, Reporter</term>
<term>Humans</term>
<term>Hydrogen-Ion Concentration</term>
<term>Macromolecular Substances</term>
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<div type="abstract" xml:lang="en">Chitosans of high molecular weights have emerged as efficient nonviral gene delivery systems, but the properties and efficiency of well-defined low molecular weight chitosans (<5 kDa) have not been studied. We therefore characterized DNA complexes of such low molecular weight chitosans and related their physical shape and stability to their efficiency as gene delivery systems in vitro and in vivo.</div>
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<Day>19</Day>
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<Title>The journal of gene medicine</Title>
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<ArticleTitle>Relationship between the physical shape and the efficiency of oligomeric chitosan as a gene delivery system in vitro and in vivo.</ArticleTitle>
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<AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Chitosans of high molecular weights have emerged as efficient nonviral gene delivery systems, but the properties and efficiency of well-defined low molecular weight chitosans (<5 kDa) have not been studied. We therefore characterized DNA complexes of such low molecular weight chitosans and related their physical shape and stability to their efficiency as gene delivery systems in vitro and in vivo.</AbstractText>
<AbstractText Label="METHODS" NlmCategory="METHODS">Individual complexes between six different chitosan oligomers (6-, 8-, 10-, 12-, 14- and 24-mers) and fluorescence-labeled T4 DNA were visualized and classified into six physical shapes using video-enhanced fluorescence microscopy. The effects of chitosan chain length, charge ratio (+/-) and solvent properties (pH and ionic strength) on the stability and structure of the complexes were studied. Gene expression in vitro and in vivo were studied using a luciferase reporter gene.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">Free DNA appeared as extended coils. Chitosan complexes had a variety of physical shapes depending on the experimental conditions. In general, the fraction of complexes that had nonaggregated, globular structures increased with increasing chain length of the chitosan oligomer, increasing charge ratio and reduction of pH (from 6.5 to 3.5). A further increase in charge ratio for globular complexes or a further reduction in pH (to 2.5) increased the fraction of aggregates, indicating a window where pharmaceutically desirable globules are obtained. Gene transfection efficiencies in vitro and in vivo were related to the physical shape and stability of the complexes. Only the 24-mer formed stable complexes that gave a high level of gene expression comparable to that of high molecular weight ultrapure chitosan (UPC) in vitro and in vivo.</AbstractText>
<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Chitosan oligomers form complexes with DNA in a structure-dependent manner. We conclude that the 24-mer, which has more desirable physical properties than UPC, is more attractive as a gene delivery system than the conventional high molecular weight chitosans.</AbstractText>
<CopyrightInformation>Copyright 2002 John Wiley & Sons, Ltd.</CopyrightInformation>
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