Biomedical Engineering Reference
In-Depth Information
In addition, network-type poly(amino esters) (n-PAE) have been prepared by
Park et al. to prolong the degradation of polyplexes based on poly(amino ester).
n-PAE exhibited transfection efficiency superior to that of PEI25, particularly in the
presence of serum (Lim et al.
2002
). Additional conjugation of n-PAE with either
aminohexanoic acid or lysine gave rise to polymers with minimal toxicity and high
transfection capability comparable to that of PEI25 (Kim et al.
2005a, 2006a
).
Furthermore, the unique feature of slow degradation of these polymers could retain
the polyplexes for 5-10 days, which makes them reliable for long-term therapeutic
applications (Kim et al.
2007a
).
3.5.4
Polyphosphoesters and Polyphosphoramidates
Polyphosphoester and polyphosphoramidates are another type of biodegradable
gene carriers, which are frequently synthesized by the ring-opening polymerization
of 4-methyl-2-oxo-2-hydro-1,3,2-dioxaphospholane followed by chlorination, then
substitution with either an alcohol or amine (Penczek and Pretula
1993
). Their
degradability is based on the hydrolytic cleavage of phosphoester bonds at physi-
ological pH (Wang et al.
2001
).
Poly(2-aminoethylpropylene phosphate) (PPE-EA, Fig.
4d
) is a water soluble
and biodegradable polyphosphoester that can be hydrolyzed into propylene glycol,
phosphate and ethanolamine in physiological condition. Following intramuscular
injection to mice, PPE-EA showed better tissue compatibility and significantly
lower cytotoxicity compared to PEI25 and PLL. Stable polyplexes could be formed
by PPE-EA and pDNA, while intact DNA could be released by incubation in PBS,
due to the degradation of PPE-EA. In the presence of chloroquine, PPE-EA showed
much higher transfection efficiency than PLL (Wang et al.
2001
). Intramuscular
injection of polyplexes derived from PPE-EA and p43-LacZ resulted in enhanced
b-galactosidase expression in anterior tibialis muscle of Balb/c mice, as compared
with naked DNA injections (Wang et al.
2002c
).
Polyphosphoramidate (PPA) bearing a spermidine side chain (PPA-SP, Fig.
4e
)
has also been synthesized by Mao and coworkers (Wang et al.
2002b
). PPA-SP could
be efficiently condense pDNA and showed lower cytotoxicity than PLL and PEI25
in COS-7 cells. In the presence of chloroquine, PPA-SP mediated transgene expres-
sion was greatly enhanced, and the optimized PPA-SP/DNA polyplexes yielded gene
expression levels close to PEI25/DNA complexes. To establish the structure-activity
relationship, PPAs with an identical backbone, same spacer group, similar molecular
weights but different charge groups containing primary to quaternary amino groups
were synthesized. Consistent with the buffering capacity, PPA with ethylenediamine
(PPA-EA) as charged groups gave the highest transfection efficiency in various cell
lines, among all the PPAs. PPA-EA also mediated the highest transgene expression
in the rat spinal cord following intrathecal injection, which was comparable to that
of PEI25. These results indicated that PPA vectors with primary amino group side
chains are more potent than those with secondary, tertiary or quaternary amino
groups for both
in vitro
and
in vivo
gene delivery (Wang et al.
2004b
).
Search WWH ::
Custom Search