Cationic Polymers for the Delivery of Therapeutic Nucleotides - Nanotechnology for the Delivery of Therapeutic Nucleic Acids - page 42

residues in the polymeric structure. Complexes formed protect the
nucleic acid from degradation.

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Dendrimers are prepared either by divergent (starting from
a central core molecule) or convergent (starting with what will
become the periphery of the molecule, building inwards) strategies.
The degree of branching is expressed in the generation of the
dendrimer. PAMAM Starburst dendrimers of generation G3 to G10
were found to form stable complexes with DNA, but their ability to
transfect different cell lines varied considerably. Higher-generation
dendrimers (G5 to G10) were found to be of superior efficiency.

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The structure of dendrimer shows high densities of amines
in the periphery of the molecule. These outer amines enable
efficient condensation of nucleic acids, leaving the inner amine
functions available for a proton sponge effect during endolysosomal
acidification, thus enabling more efficient endosomal escape. An
increased flexibility of the polymer with a better ability to complex
DNA might play a crucial role.

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Dendrimer delivery systems are
useful and less toxic because they can be modified to have

defined molecular mass, defined molecular size and shape for
avoiding biological barriers.

in vivo

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2.3.5 Other Cationic Polymers

Includes cationic polyesters, poly(amino ester)s, poly(amidoamine)s,
etc.

2.3.5.1 Cationic polyesters

Polyesters have hydrocarbon backbones that contain ester func-
tional groups or linkages. Some of the commonly used polyesters
and their copolymers for gene delivery mechanisms include
polyhydroxyalkanoate (PHA), polycaprolactone (PCL), polyglycolide
or polyglycolic acid (PGA), and polylatic acid (PLA). PHA is biological
polyesters produced by microorganisms. PHA have gained major
importance due to their structural diversity and close analogy to
plastics. Additionally, these are also biodegradable and show good
biocompatibility.
Considering polyester copolymers, poly(4-hydroxy-L-proline)
ester (PHP) is an water soluble polycationic biodegradable polymeric
gene carrier. PHP ester forms a strong complex with DNA by means
of electrostatic interaction. Transfection of β-galactosidase gene