Gene Delivery Using Chemical Methods - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 171

peptide and the cell membrane, which destabilize the membrane and deliver the pep-
tide into the cytoplasm [282] .
Early studies of pAntp-mediated ODN delivery showed effective cellular uptake
and transfection efficiency with minimal cytotoxicity. However, its transfection effi-
ciency was lower than Lipofectin TM [283] . Pritchard et al. overcame this drawback by
conjugating pAntp with L4F, a water-soluble amphipathic peptide with a high-binding
affinity for lipids (Asp-Trp-Phe-Lys-Ala-Phe-Tyr-Asp-Lys-Val-Ala-Glu-Lys-Phe-
Lys-Glu-Ala-Phe). The ternary complex of pAntp-L4F, DNA, and Lipofectamine TM
displayed higher transfection efficiency than either of the peptide-DNA conjugates
or the Lipofectamine TM 2000-DNA complex [284] . In another study, nanoparticles
of DNA-polymer-pAntp were explored for gene delivery in brain capillary endo-
thelial cells (BCEC). It was shown that pAntp was able to enhance gene transfer
efficiency in BCECs only for polyplexes capable of delivering DNA on their own
(PEI-DNA and PAMAM-DNA) [285] .
4.6 Dendrimers
Dendrimers are small, monodisperse, symmetrical, and highly branched macro-
molecules first discovered in the early 1980s by D. Tomalia et al. [286,287] . Each
dendrimer unit is composed of a central core with a series of symmetrically formed
branches around the core. Functionality of the branching units is generally two or
three, which makes the layer of branching units doubles or triples. Dendrimers differ
in their initiator structure and in the number of layers of the building blocks in each
molecule. The number of layers is also called the number of generations, designated
by G0, G1, and G2. The size of the dendrimers is generally determined by the num-
ber of layers or generations present in the polymer [288] .
Dendrimers are symmetrical, three-dimensional, hyperbranched arrays of den-
drons. There are two synthetic approaches that have been used for the preparation
of dendrimers: the convergent approach and the divergent approach [289] . They can
be synthesized in either way; starting from the core molecules and going out to the
periphery by connecting the branch groups or by forming the branches first and then
connecting all around the core. Dendrimers synthesize by the divergent approach,
which takes place in a geometrically outward fashion, resulting in a branched poly-
mer with spherical geometry and containing interior tertiary and exterior primary
amines. After every reaction on the initiator core of the dendrimer, the generational
number increases by one. The commonly used initiators comprise ammonia (NH 3 ) as
a trivalent initiator and ethylenediamine as a tetravalent initiator. The interior cavity
of dendrimers is very suitable for the encapsulation of small molecules like DNA.
In addition, multiple valencies, a high degree of branching, a globular architecture,
and defined molecular weight make dendrimers promising vectors for gene delivery.
Greater ease of handling, manufacturing, and functionalization are attractive fea-
tures for scale up and large-scale production. The most distinguished feature is that
they can be manipulated to present multiple copies of surface groups for biological
reorganization of specific cells. Among the many different structural designs used