Lipoplexes and Polyplexes: From Gene Delivery to Gene Expression - Nanotechnology for the Delivery of Therapeutic Nucleic Acids - page 4

The +/- cationic lipid/DNA charge ratio predetermines the
size and shape of the formed complexes. At low +/- charge ratio,
DNA molecules are partially “decorated” by the cationic lipid, thus
a strong propensity to aggregation is observed in the complexes
that result in micrometric particles with low transfection efficiency.
On the other hand, at high +/- charge ratio, DNA is highly packed
in multi-lamellar bilayer particles of about 90-300 nm as shown in
Fig. 1.1. These types of particles are the most efficient for gene
delivery to cells.
For more than 10 years, the design, synthesis, and characteriz-
ation of novel cationic lipids and polymers for increased gene delivery
and transgene expression have been our central preoccupation. Most
of the topics summarized here deal with lipopolyamines/cationic
lipids or systems containing them (lipoplexes) and some polymers
(polyplexes) or dendrimers (dendriplexes).

1. Lipopolyamines

Cationic lipids are composed of three elements: from one side a
cationic entity, for example amines, quaternary ammonium salts,
etc., from the other side a lipid entity usually a double lipid chain,
cholesterol, etc., and, in between, a linker entity that brings together
the other elements. In our works, we have implemented a step-by-
step strategy by introduction of systematic modifications into the
cationic lipid backbone and the introduction of a “side chain entity”
on the linker (see Fig. 1.2).

Cation Hydrophobic

entity

Linker

Variable length and
side chain entity

Geometry
modification

Chain length
modification

Figure 1. Structure-activity relationship studies of lipopolyamines.