Biomedical Engineering Reference
In-Depth Information
entrapping genetic materials (such as pDNA, ODN or siRNA) via a facile method
(Kakizawa and Kataoka
2002
). It was found that when the PEG-PAA concentration
was above a certain value, monodispersed and stable nanoparticles could be
obtained, which were essential to prevent precipitation of CaP crystals during nano-
particle formation. The PEGylated CaP particles exhibited high efficiency in encap-
sulating genetic materials, and also exhibited minimal cytotoxicity, in addition to
considerable nuclease-resistance, and appreciable gene expression under optimized
conditions.
In vitro
experiments, including cellular uptake and gene knockdown,
were performed for hybrid PEG-PAA/CaP/DNA nanoparticles containing fluores-
cently labeled nucleic acid (Kakizawa et al.
2004
). By investigating the effects of
temperature and the presence of metabolic inhibitors on the uptake of the nanopar-
ticles, it was revealed that the nanoparticles were internalized via an endocytotic
pathway. Moreover, significant gene knockdown against luciferase was achieved by
the hybrid nanopaticles loaded with siRNA encoding a luciferase sequence. The
same group has proposed an environmentally responsive siRNA delivery system
based on CaP nanostructures (Zhang et al.
2009
). Block copolymers consisting of
PEG and siRNA were utilized to prepare CaP nanoparticles, in which the PEG and
siRNA segments were linked via a disulfide bond that can be reversibly cleaved in
the presence of reducing reagents. Due to the environmental sensitivity, the PEG
shell layer would be selectively cleaved off from the hybrid nanoparticles when
located inside the intracellular compartments with a reducing environment, upon
cellular uptake. This study clearly demonstrated that PEGylated CaP nanocarrier
may be a promising candidate for
in vivo
gene delivery applications.
5.7
Layered Double Hydroxides/Clays
Layered double hydroxides (LDH), also known as hydrotalcite materials or
anionic clays, are a family of clays which contain positively charged layers, exem-
plified by the natural mineral hydrotalcite [Mg
6
Al
2
(OH)
16
CO
3
· 4H
2
O]. Most LDH
materials can be described using the general formula
( )
( )
x
+
é
II
III
ù
m
-
M M OH
A
×
ë
û
1x x
-
2
x/m
(
)
=- =-
, where M
II
represents a divalent metal cation,
M
III
a trivalent metal cation and A
m-
an anion (Itoh et al.
2005
). LDH materials can
be found in nature as minerals or readily synthesized in the laboratory (Braterman
et al.
2004
). Most widely used method for LDH preparation is called co-precipita-
tion method. This procedure includes mixing an aqueous solution containing the
salts of two metal ions with a base solution in the presence of the desired anion to
nucleate and grow the metal hydroxide layers. Metal chlorides or nitrates are gener-
ally used (Yamaoka et al.
1989
; Braterman et al.
2004
). Additionally, because the
anions present in the LDH interspaces are exchangeable, thus anion exchange is the
second most widely used method for the synthesis of LDH hybrids (Crepaldi et al.
1999
). Anion exchange is simply accomplished by stirring previously formed LDH
materials in solution that contains the replacement anion species. Other methods for
nH O x
0.2
0.4; n
0.5
1
2
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