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

Cationic lipid-DNA complexes are used as gene transfer vehicles in molecula r biology and potentially in human gene therapy. In recent synchrotron X-ra y scattering studies the molecular structure of such self-assembling aggreg ates was elucidated. A rich polymorphism of lamellar; hexagonal, lamellar-c olumnar and micellar mesophases was found. In this article we describe comp osite phases of cationic lipid mixed with hyaluronic acid and dextran sulfa te which likewise form intercalated lamellar complexes. Heterogeneous phase s of lipid/dextran sulfate mixed with lipid/DNA exhibit macroscopic phase s eparation. When dextran sulfate is added to preformed cationic lipid DNA co mplexes the latter are dissolved in favor of the lipid-polyelectrolyte phas es. We investigated the kinetics of the DNA replacement by dextran sulfate. The experiments are intended to mimic the interaction of cationic lipid ge ne delivery complexes with highly charged extracellular matrix components.