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Mechanistic studies on aggregation of polyethylenimine‐DNA complexes and its prevention
Author(s) -
Sharma Vikas K.,
Thomas Mini,
Klibanov Alexander M.
Publication year - 2005
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.20444
Subject(s) - polyethylenimine , chemistry , ionic strength , viscosity , dna , hydrophobic effect , biophysics , transfection , gene delivery , chemical engineering , organic chemistry , biochemistry , gene , aqueous solution , materials science , biology , engineering , composite material
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.