Lipid-DNA and lipid-polyelectrolyte mesophases: structure and exchange kinetics

Cationic lipid-DNA complexes are used as gene transfer vehicles in molecular biology and potentially in human gene therapy. In recent synchrotron X-ray scattering studies the molecular structure of such self-assembling aggregates was elucidated. A rich polymorphism of lamellar, hexagonal, lamellar-columnar and micellar mesophases was found. In this article we describe composite phases of cationic lipid mixed with hyaluronic acid and dextran sulfate which likewise form intercalated lamellar complexes. Heterogeneous phases of lipid/dextran sulfate mixed with lipid/DNA exhibit macroscopic phase separation. When dextran sulfate is added to preformed cationic lipid DNA complexes the latter are dissolved in favor of the lipid-polyelectrolyte phases. We investigated the kinetics of the DNA replacement by dextran sulfate. The experiments are intended to mimic the interaction of cationic lipid gene delivery complexes with highly charged extracellular matrix components.