Cationic polysaccharides for gene delivery

Tony Azzam, Arthur Raskin, Arik Makovitzki, Henry Brem, Pierre Vierling, Michal Lineal, Abraham J. Domb

Research output: Contribution to journalArticle

Abstract

Cationic polysaccharides based on spermine-dextran conjugates were synthesized and tested as vectors for gene transfection. Dextrans of 10-380 kDa were oxidized under mild conditions by potassium periodate to obtain the respective polyaldehydes in 90% overall yield. The oxidized dextrans were reacted by reductive amination with increasing amounts of spermine, and the efficacy of conjugation between the oligoamine and polysaccharides was studied as a function of spermine/aldehyde mole ratio, pH, and temperature of medium. The optimal conjugation yields were obtained at 1.25 mole ratio (spermine/aldehyde groups) and pH 11 at room temperature. Under these conditions, ∼2 μmol/mg (spermine/polysaccharide) conjugation was achieved with 25-30% of the spermine moieties were conjugated in both sides to form branched polymers. The water-soluble polymers obtained were interacted with pCMV-GFP plasmid to form nanoparticles that were introduced to HEK293 and NIH3T3 cells in vitro for transfection efficacy assessment. Out of about 50 different polymer structures, only spermine-dextran of 6000-8000 Da, spermine content of ∼2 ∼mol/mg, and degree of branching of 25-30% was active in transfecting about 50% of the cells while all other polymers were significantly less active.

Original languageEnglish (US)
Pages (from-to)9947-9953
Number of pages7
JournalMacromolecules
Volume35
Issue number27
DOIs
StatePublished - Dec 31 2002

    Fingerprint

ASJC Scopus subject areas

  • Organic Chemistry
  • Polymers and Plastics
  • Inorganic Chemistry
  • Materials Chemistry

Cite this

Azzam, T., Raskin, A., Makovitzki, A., Brem, H., Vierling, P., Lineal, M., & Domb, A. J. (2002). Cationic polysaccharides for gene delivery. Macromolecules, 35(27), 9947-9953. https://doi.org/10.1021/ma0209592