Mechanistic studies on aggregation of polyethylenimine-DNA complexes and its prevention

Authors

  • Vikas K. Sharma,

    1. Department of Chemistry and Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
    Search for more papers by this author
  • Mini Thomas,

    1. Department of Chemistry and Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
    Search for more papers by this author
  • Alexander M. Klibanov

    Corresponding author
    1. Department of Chemistry and Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
    • Department of Chemistry and Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
    Search for more papers by this author

Abstract

Aggregation of polyethylenimine (PEI)-DNA complexes severely undermines their utility for gene delivery into mammalian cells. Herein we undertook to elucidate the mechanism of this deleterious phenomenon and to develop rational strategies for its prevention. The effect of temperature, surfactants, complex concentration, ionic strength, viscosity, and pH on the time course of this aggregation was systematically examined. The aggregation process was completely inhibited by 2.5% polyoxyethylene (100) stearate (POES) and to a lesser degree by other nonionic surfactants. Importantly, POES preserved the transfection efficiency of the complexes without inducing toxicity. The aggregation was also reduced by lowering the temperature and pH, diluting the complexes, and increasing the solution viscosity. It is concluded that PEI-DNA complexes aggregate primarily due to hydrophobic interactions, while electrostatic attractions play little role. © 2005 Wiley Periodicals, Inc.

Ancillary