424
R. Mankamna Kumari et al.
PEGylation several other modifications and substitutions of PEI have been investigated. PLGA incorporated PEI NPs not only showed better in vivo transfection but
also proved to be a suitable vector for DNA vaccination (Bivas-Benita et al. 2009;
Chumakova et al. 2008). In a recent study, lPEI was substituted by hydroxyethyl with
a degree of substitution varying from 15% to 45%. It was observed that even after the
loss of ionizable amines, there was a subsequent increase in pH-independent solubility and buffering capacity. Further, it reduced erythrocyte aggregation, hemolytic
potential, in vitro cytotoxicity, and efficient mRNA knockdown (Patil et al. 2018).
Multidrug resistance is another common trouble faced in the field of cancer therapeutics. This phenomenon is mediated by the overexpression of P-glycoproteins (P-gp)
that plays an important role in resistance to chemotherapy. This plasma membrane
glycoprotein causes efflux of major chemotherapeutic drugs such as vinblastine, doxorubin, and paclitaxel (Perez 2009; Riordan et al. 1985; Wind and Holen 2011). P-gp
inhibitors are commonly employed to circumvent the problem; however, they are
associated with certain side effects such as toxicity, off target distribution and other
pharmacokinetic interactions. In a study, phospholipid modified PLGA NPs carrying
siRNA against P-gp was introduced in breast cancer. First, DOPE-PEI nanocarriers
with PEG coating was introduced in breast tumor model that showed 8% injected
dose accumulation in the tumor owing to its property of enhanced permeability retention effect (EPR). In the second experiment, DOPE-PEI/siRNA along with Doxorubicin showed decreased tumor volume by threefold versus control with specific P-gp
downregulation (Essex et al. 2015). In a similar type of study, siRNA was targeted
against Multidrug resistance-associated protein 1 (MRP1) via PEI capped porous
silica NPs. The nanoformulation showed optimized release profile and proved to
be biocompatible, better cellular uptake, and effective knockdown of MRP1. With
these, there was a profound decrease in the reduction of glioblastoma multifome
(GBM) proliferation. The formulation also displayed positive result in mice with
significant 82% reduction in the protein level 48 h post injection. In addition, there
was no histopathological signs of acute damage in the organs (Tong et al. 2018).
The miRNAs also have a role in cancer. To inhibit its activity, short seed-directed
LNA oligonucleotides (12- or 14-mer antiseeds) were introduced for miRNA inhibition. It was observed that miRNA against miR-17-5p and miR-20a downregulated
the expression of p21 expression than any other miRNA hairpin inhibitors (Thomas
et al. 2012).
3.4 Dendrimers
Dendrimers are polymers possessing a core connected to polymer branches, where
different molecules are conjugated at its terminals. It is inherently hydrophilic
that makes it a good candidate for the delivery of therapeutic molecules including hydrophobic drugs. The small size of polymer (<15 nm) further makes it a
suitable candidate for its delivery into tumour through EPR effect. Polyamidoamine
R. Mankamna Kumari et al.
PEGylation several other modifications and substitutions of PEI have been investigated. PLGA incorporated PEI NPs not only showed better in vivo transfection but
also proved to be a suitable vector for DNA vaccination (Bivas-Benita et al. 2009;
Chumakova et al. 2008). In a recent study, lPEI was substituted by hydroxyethyl with
a degree of substitution varying from 15% to 45%. It was observed that even after the
loss of ionizable amines, there was a subsequent increase in pH-independent solubility and buffering capacity. Further, it reduced erythrocyte aggregation, hemolytic
potential, in vitro cytotoxicity, and efficient mRNA knockdown (Patil et al. 2018).
Multidrug resistance is another common trouble faced in the field of cancer therapeutics. This phenomenon is mediated by the overexpression of P-glycoproteins (P-gp)
that plays an important role in resistance to chemotherapy. This plasma membrane
glycoprotein causes efflux of major chemotherapeutic drugs such as vinblastine, doxorubin, and paclitaxel (Perez 2009; Riordan et al. 1985; Wind and Holen 2011). P-gp
inhibitors are commonly employed to circumvent the problem; however, they are
associated with certain side effects such as toxicity, off target distribution and other
pharmacokinetic interactions. In a study, phospholipid modified PLGA NPs carrying
siRNA against P-gp was introduced in breast cancer. First, DOPE-PEI nanocarriers
with PEG coating was introduced in breast tumor model that showed 8% injected
dose accumulation in the tumor owing to its property of enhanced permeability retention effect (EPR). In the second experiment, DOPE-PEI/siRNA along with Doxorubicin showed decreased tumor volume by threefold versus control with specific P-gp
downregulation (Essex et al. 2015). In a similar type of study, siRNA was targeted
against Multidrug resistance-associated protein 1 (MRP1) via PEI capped porous
silica NPs. The nanoformulation showed optimized release profile and proved to
be biocompatible, better cellular uptake, and effective knockdown of MRP1. With
these, there was a profound decrease in the reduction of glioblastoma multifome
(GBM) proliferation. The formulation also displayed positive result in mice with
significant 82% reduction in the protein level 48 h post injection. In addition, there
was no histopathological signs of acute damage in the organs (Tong et al. 2018).
The miRNAs also have a role in cancer. To inhibit its activity, short seed-directed
LNA oligonucleotides (12- or 14-mer antiseeds) were introduced for miRNA inhibition. It was observed that miRNA against miR-17-5p and miR-20a downregulated
the expression of p21 expression than any other miRNA hairpin inhibitors (Thomas
et al. 2012).
3.4 Dendrimers
Dendrimers are polymers possessing a core connected to polymer branches, where
different molecules are conjugated at its terminals. It is inherently hydrophilic
that makes it a good candidate for the delivery of therapeutic molecules including hydrophobic drugs. The small size of polymer (<15 nm) further makes it a
suitable candidate for its delivery into tumour through EPR effect. Polyamidoamine