Hydrophobized dextran-spermine conjugate as potential vector for in vitro gene transfection

Tony Azzam, Hagit Eliyahu, Arik Makovitzki, Michal Linial, Abraham J. Domb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

Dextran polysaccharide was grafted by reductive-amination with mixtures of spermine and other natural/synthetic oligoamines of two to four amine groups. The transfection efficiencies of the polycations thus obtained were assessed in various cell lines, and found to depend on the spermine contents. Higher spermine ratios of grafted oligoamines resulted in high gene expression, whereas low to negligible expressions were obtained with lower spermine contents. The effect was explained by spermine residues which exhibit altered buffering capacity in comparison to other substituted oligoamines. Hydrophobization of dextran-spermine (D-SPM) was achieved by treating the polymer with N-hydroxysuccinimide derivatives of cholesterol and fatty acids in a mixture of water/THF. The degree of hydrophobization was in the range of 1-30% mol/mol (hydrophobic moieties/primary amine) and the coupling yields were >95% as determined by 1H-NMR. The oleate-modified D-SPM remarkably enhanced the gene expression in serum rich media, in marked contrast to unmodified D-SPM which resulted with a drastic decrease in the transfection yields. Modified D-SPM derivatives of other fatty acids and cholesterol showed improved transfection yields in comparison to unmodified D-SPM, but to a lower extent when compared to oleate modification. The improvement in cell transfection was attributed to oleate residues which probably play a role in increasing stability and uptake of polycation-DNA complexes.

Original languageAmerican English
Pages (from-to)309-323
Number of pages15
JournalJournal of Controlled Release
Volume96
Issue number2
DOIs
StatePublished - 28 Apr 2004

Bibliographical note

Funding Information:
Tony Azzam is grateful to the Ministry of Science, Israel, for the financial assistance. This work was supported in part by the AFIRST, French–Israeli Cooperation on Gene Therapy, and by the US–Israel Binational Fund (BSF).

Keywords

  • Dextran
  • Gene delivery
  • Hydrophobic
  • Reductive-amination
  • Spermine

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