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Dicationic gemini surfactant gene delivery complexes contain cubic-lamellar mixed polymorphic phase

M. Foldvari, S. Wettig, I. Badea, R. Verrall and M. Bagonluri
University of Saskatchewan, CA

Keywords:
gemini surfactant, SAXS, gene therapy, skin, cubic phase

Abstract:
The characterization of structural properties of novel dicationic (gemini) surfactant-based DNA complexes as micro/nano-scale self-assembling delivery systems for cutaneous gene therapy is described and discussed as related to measured transfection efficiencies. Previous small-angle x-ray scattering (SAXS) studies indicated that gemini surfactants with shorter (n=3-4) spacers induce polymorphic structures in the generally lamellar complexes, and exhibit greater transfection activity and cutaneous delivery. In this study we further elucidated the structural properties of the complexes by SAXS. We have identified the Pn3m cubic phase in DNA-gemini-DOPE complexes with gemini surfactants having 12, 16 and 18:1 alkyl tail length. Increasing gemini/DNA charge ratios from 0.5 to 10 resulted in increasingly mixed (Pn3m and HII or Pn3m and L) polymorphic systems with lamellar (L) features becoming more predominant. DNA-gemini complexes (without DOPE) exhibited very weak single scattering peaks representative of gemini- plasmid particles with no long range order and low transfection efficiency. In gemini – DOPE complexes (no DNA) the main complex geometry is inverted hexagonal (HII) at low concentrations of gemini, with weakly ordered systems (generally lamellar) observed at increased concentrations. Overall, the presence of the newly identified cubic Pn3m phase in the DNA-gemini-DOPE complexes appears to be advantageous for increased transfection efficiency.

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