Cationic Polymers for the Delivery of Therapeutic Nucleotides - Nanotechnology for the Delivery of Therapeutic Nucleic Acids - page 36

applications due to relatively low competency. Low cytotoxicity and
high gene transfection efficiency are critical issues in designing non-
viral gene delivery vectors. Therefore, PLL are modified primarily
at the reactive primary amino groups of the lysine residues as
side chains with various functional hydrophobic groups such as
thiol and histidyl moieties.

42

To improve aqueous solubility of
PLL/DNA complexes, reductive amination of amino groups of PLL
and the reductive ends of hydrophilic dextran were reported.

43, 44

Accordingly, PLL was glycosylated using methylglycolate to decrease
cytotoxicity.

45

reported covalent linking PLL to PEG to
decrease both cytotoxicity and aggregation of PLL.

Choi et al.

46
To produce reducible, effective biocompatible, and non-
toxic gene delivery system, Nounou designed and synthesized

novel reducible linear L-lysine modified copolymers (LLC). The
transfection efficiencies of the polyplexes showed that LLC polyplexes
produced five times higher transfection efficiencies in HDF cells,
three times higher transfection efficiencies in MCF-7 cells, and four
times higher transfection efficiencies in MA cells as compared to
the optimal PLL control. The LLC/pDNA polyplexes showed
significantly lower cytotoxicity in HDF, MCF-7, and MA cells.
These results suggest that these LLC are efficient, reducible, and
biocompatible polymers for gene delivery.

et al.

47

synthesized novel biodegradable poly(lactic acid)-
poly(ethylene glycol)-poly(L-lysine) (PLA-PEG-PLL) copolymer, and
explored its applicability and feasibility as a non-viral vector for gene
transport. The physicochemical properties (morphology, particle
size, and surface charge) and the biological properties (protection
from nuclease degradation, plasma stability,

Fu et al.

in vitro cytotoxicity,

and transfection ability) of the gene-loaded PLA-PEG-

PLL nanoparticles were evaluated and reported as very attractive
candidate as a non-viral vector for gene delivery

in vitro

48
Bone marrow stromal cells (BMSC) represent an important
cell phenotype for pursuit of successful gene therapy. Farrell

in vivo .

et al.

compared PLL and branched PEI as gene carriers for modification
of BMSC. Although both PLL and PEI were readily internalized with
BMSC, but the relative uptake of PEI was significantly higher as
compared to the PLL, but both PLL and PEI readily displayed cellular
uptake.

49

investigated the relationships between
structures of PLL molecules with respect to their gene delivery

Yamagata et al.