Biomedical Engineering Reference
In-Depth Information
properties such as easily modified particle size, loading capacity, affinity
to nucleic acid, biodegradability, and biocompatibility (Zhang, Wu, et al.
2010; Bongio et al. 2011; Holmquist et al. 2011). CaP materials have shown
increased transfection efficacy as compared to naked plasmid DNA trans-
fection
in vitro
and
in vivo
. Due to the uncertainty in CaP-DNA complex syn-
thesis acted by pH, temperature, and butter conditions, the idea of applying
CaP-DNA coprecipitation with organic polyplexes such as PEG, PLG, PVA,
chitosan, and liposome was proposed and brought out high transfection effi-
ciency and low toxicity (Fu et al. 2005; Ramachandran et al. 2009; Choi and
Murphy 2010; Kimura et al. 2011).
To confirm the hybrid materials and nucleic acid to be an integrated gene
delivery system, many methods are enrolled. Transmission electron micro-
scopic (TEM) observation demonstrated the hybrid structure participated
with CaP (Zohra et al. 2009). Scanning electron microscopic observation and
dynamic light scattering measurement indicated that HAps were obviously
encapsulated in the fabricated PVA/HAp/DNA nanoparticles (Kimura et al.
2011). Differential scanning calorimetry (DSC) suggested the existing inter-
action among each component of DNA-calcium-phosphate (CaPi-pDNA)
complexes and the polymeric matrices of PLGA (Tang et al. 2012).
X-ray dif-
fractometry (XRD) further proved the conclusion that the CaPi-pDNA was in
weak crystallization form inside the nanoparticles.
Several studies have focused on the factors to enhance the transfection
efficiency. The intrinsic properties of the CaP mineral coating and the sur-
rounding solution conditions are supposed to be the pacing factors in the
release of plasmid DNA (Choi and Murphy 2010). The effect of the molecular
weight, composition of organic phase, initial concentration of calcium phos-
phate, and Ca/P ratio were traversed based on a CaPi-pDNA-PLGA gene
delivery system (Tang et al. 2012). The researcher demonstrated the opti-
mal formulation to be spherical in shape, 207±5 nm in size, and 95.7%±0.8%
in entrapment efficiency. In addition, in another control study, apparently
higher gravitational force rooted in the applying inorganic carbonate apatite
enhanced initial steps of cellular contact and internalization of mRNA com-
pared to separate cationic liposome (Zohra et al. 2009).
Crucially, the combined application of organics and CaP made up weak-
nesses mutually. To prevent the fast crystallization of CaP, which is the main
factor for the transfection efficiency, Kakizawa et al. (2004)
introduced a
novel self-assembly of poly(ethylene glycol)-block-poly(asparticacid) block
copolymers (PEG-P(Asp)) with CaP hybrid nanoparticles. Nevertheless, the
application of chroloquin functioning as an endosomal-escape promoter has
been restricted. In this regard, a modified strategy was brought out with
poly(methacrylic acid) (PMA) in use revealing excellent colloidal stability
and serum tolerability attribute to the steric stabilization effect of the PEG
palisade (Kakizawa et al. 2006). To promote cell adhesion onto the hybrid
layer, fibronectin was fabricated with supersaturated calcium phosphate
solution supplemented with BMP-2 DNA and in this way enhanced gene
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