Improved stability and efficacy of chitosan/pDNA complexes for gene delivery

Biotechnol Lett. 2015 Mar;37(3):557-65. doi: 10.1007/s10529-014-1727-7. Epub 2014 Nov 12.

Abstract

Among polymeric polycations, chitosan has emerged as a powerful carrier for gene delivery. Only a few studies have focused on the stability of the chitosan/DNA complex under storage, although this is imperative for nanomedicinal applications. Here, we synthesized polyelectrolyte complexes at a charge ratio of 10 using 50 kDa chitosan and plasmid (p)DNA that encodes a GFP reporter. These preparations were stable up to 3 months at 4 °C and showed reproducible transfection efficiencies in vitro in HEK293 cells. In addition, we developed a methodology that increases the in vitro transfection efficiency of chitosan/pDNA complexes by 150% with respect to standard procedures. Notably, intracellular pDNA release and transfected cells peaked 5 days following transection of mitotically active cells. These new developments in formulation technology enhance the potential for polymeric nanoparticle-mediated gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chitosan / metabolism*
  • DNA / metabolism*
  • Drug Stability
  • Epithelial Cells / metabolism
  • Gene Transfer Techniques*
  • Humans
  • Plasmids*
  • Reproducibility of Results
  • Temperature
  • Time Factors
  • Transfection / methods*
  • Transformation, Genetic

Substances

  • DNA
  • Chitosan