Application of Nanotechnology in Diagnosis and Therapeutics
423
cell lines (bEnd.3 and astrocytes). The nanoformulation was tested both in vitro
and in vivo. Results showed reduced β-amyloid plaques and inflammation of AD
(Sánchez-López et al. 2018). With the increasing use of phytochemicals, curcumin
was also utilized for the treatment of AD (Fan et al. 2018).
3.3 Polyethylenimine
Polyethylenimine is a polycationic molecule, that occur in the form of branched
(with primary, secondary, and tertiary amines) or linear isomers (lPEI). The polymer
has emerged as a favorable vector for the delivery of nucleic acids (NA) at low cost.
Branched PEI (bPEI) was first introduced in the year 1995. It soon flourished as a
promising vector for transfection studies using oligonucleotides (Bandyopadhyay
et al. 1999), plasmids (Liu et al. 2009), and ribozymes (Aigner et al. 2002). bPEI
and lPEI behave differently in terms of DNA compactability (Boussif et al. 1995),
nuclear uptake (Brunner et al. 2000, 2002), and biological performance (Wightman
et al. 2001). For example BPEI forms a stable and smaller sized NPs with more
transfectability, whereas lPEI forms NPs of size near micrometer range with more
tendency to form aggregation (Goula et al. 1998; Wightman et al. 2001). However,
lPEI is known to be less toxic that was seen to exhibit tenfold higher expression of
luciferase activity upon nasal instillation in mice (Grosse et al. 2008). The difference
in the behavior of bPEI and lPEI could be attributed to the polyplex preparation,
administration routes, and other conditions. In addition, nanocomplexes could be
delivered by utilizing targeting ligands as discussed in the earlier sections. In one of
the studies, hyaluronic acid (HA)-PEI (HA-PEI) conjugate was used for the delivery
of siRNA complexes to B16F1 cells expressing hyaluronan receptor-1 (LYVE-1).
This showed higher luciferase activity in relative to non-LYVE-1 expressing cell
lines (Jiang et al. 2008a). PEGylation of PEI NPs also proved to be beneficial with
reduced drawbacks. Unmodified PEI NPs carrying NA shows less efficacy in vivo
conditions. This could be attributed to its interaction with serum proteins such as
albumin, fibrinogen, IgD, IgM, apolipoproeins, and components of compliment system (Ahn et al. 2002; Nguyen et al. 2000; Plank et al. 1996; Tang et al. 2003). The
polyplexes get cleared by reticuloendothelial system. Thereby, reducing its plasma
circulation life. PEGylation subsequently increased the solubility, blood circulation
time, and decreased aggregation as well as macrophage capture (Kichler et al. 2002;
Sung et al. 2003; Vonarbourg et al. 2006). Furthermore, PEG could be conjugated to
specific ligands to improve its cellular uptake and targetability. In one of the studies, Chen et al. synthesized galactose-PEG-bPEI copolymers that exhibited 4.5–11.6
fold increase in the transfection efficiency in A549 cell line and in mice, respectively, in relative to conventional bPEI/DNA complexes (Chen et al. 2008b). Peptide
conjugated PEG-PEI NPs are also being used as a targeting ligand. Kleeman et al.
synthesized peptide-conjugated bPEI (25KDa) via hetero-bifunctional PEG spacer
(Kleemann et al. 2005). Overall, it was observed that acid-labile linkages of ligand and PEG displayed enhanced improvement of PEGylated vectors. In addition to
423
cell lines (bEnd.3 and astrocytes). The nanoformulation was tested both in vitro
and in vivo. Results showed reduced β-amyloid plaques and inflammation of AD
(Sánchez-López et al. 2018). With the increasing use of phytochemicals, curcumin
was also utilized for the treatment of AD (Fan et al. 2018).
3.3 Polyethylenimine
Polyethylenimine is a polycationic molecule, that occur in the form of branched
(with primary, secondary, and tertiary amines) or linear isomers (lPEI). The polymer
has emerged as a favorable vector for the delivery of nucleic acids (NA) at low cost.
Branched PEI (bPEI) was first introduced in the year 1995. It soon flourished as a
promising vector for transfection studies using oligonucleotides (Bandyopadhyay
et al. 1999), plasmids (Liu et al. 2009), and ribozymes (Aigner et al. 2002). bPEI
and lPEI behave differently in terms of DNA compactability (Boussif et al. 1995),
nuclear uptake (Brunner et al. 2000, 2002), and biological performance (Wightman
et al. 2001). For example BPEI forms a stable and smaller sized NPs with more
transfectability, whereas lPEI forms NPs of size near micrometer range with more
tendency to form aggregation (Goula et al. 1998; Wightman et al. 2001). However,
lPEI is known to be less toxic that was seen to exhibit tenfold higher expression of
luciferase activity upon nasal instillation in mice (Grosse et al. 2008). The difference
in the behavior of bPEI and lPEI could be attributed to the polyplex preparation,
administration routes, and other conditions. In addition, nanocomplexes could be
delivered by utilizing targeting ligands as discussed in the earlier sections. In one of
the studies, hyaluronic acid (HA)-PEI (HA-PEI) conjugate was used for the delivery
of siRNA complexes to B16F1 cells expressing hyaluronan receptor-1 (LYVE-1).
This showed higher luciferase activity in relative to non-LYVE-1 expressing cell
lines (Jiang et al. 2008a). PEGylation of PEI NPs also proved to be beneficial with
reduced drawbacks. Unmodified PEI NPs carrying NA shows less efficacy in vivo
conditions. This could be attributed to its interaction with serum proteins such as
albumin, fibrinogen, IgD, IgM, apolipoproeins, and components of compliment system (Ahn et al. 2002; Nguyen et al. 2000; Plank et al. 1996; Tang et al. 2003). The
polyplexes get cleared by reticuloendothelial system. Thereby, reducing its plasma
circulation life. PEGylation subsequently increased the solubility, blood circulation
time, and decreased aggregation as well as macrophage capture (Kichler et al. 2002;
Sung et al. 2003; Vonarbourg et al. 2006). Furthermore, PEG could be conjugated to
specific ligands to improve its cellular uptake and targetability. In one of the studies, Chen et al. synthesized galactose-PEG-bPEI copolymers that exhibited 4.5–11.6
fold increase in the transfection efficiency in A549 cell line and in mice, respectively, in relative to conventional bPEI/DNA complexes (Chen et al. 2008b). Peptide
conjugated PEG-PEI NPs are also being used as a targeting ligand. Kleeman et al.
synthesized peptide-conjugated bPEI (25KDa) via hetero-bifunctional PEG spacer
(Kleemann et al. 2005). Overall, it was observed that acid-labile linkages of ligand and PEG displayed enhanced improvement of PEGylated vectors. In addition to