Biomedical Engineering Reference
In-Depth Information
82
entangled DNA/polymer-soluble aggregates.
Further, Cao
et al.
synthesized diblock copolymers of PCL and LPEI and assembled
it to biodegradable nano-carriers for co-loading siRNA and small
molecular drug in a multifunctional hierarchical nano-assembly, for
simultaneously delivering siRNA and drug into the same cancer cells,
yielding synergistic effect of RNA interference and chemotherapy in
cancer.
103
2.5.2
siRNA Delivery
Regulation of gene expression using short interfering RNA (siRNA)
is a promising strategy for research and treatment of numerous
diseases. siRNA is a rapidly emerging class of new therapeutic
molecules for the treatment of inherited and acquired diseases.
However, poor cellular uptake and instability in physiological
conditions limit its therapeutic potential. Hence there is a need to
develop a delivery system that can protect and efficiently transport
siRNA to the target cells. Cationic delivery vectors form condensed
complexes with siRNA that, in turn, provides protection to siRNA
against enzymatic degradation and further leads to tissue and cellular
targeting. siRNA delivery has also been studied widely together with
polymers like PEI, PLL chitosan, and PEG-based polymers.
Nanoparticles derived from polymers, such as chitosan and PEI,
have found numerous applications for efficient delivery of siRNA,
owing to ease of manipulation, high stability, low cost, and high gene
carrying capability.
104
have developed and characterized
a delivery system for siRNA composed of PEI, PEG, and mannose.
PEI forms polyplexes with siRNA, PEG forms a hydrophilic layer
outside of the polyplexes for steric stabilization, and mannose
serves as a cell binding ligand for macrophages. PEGylation of the
PEI reduced toxicity without any adverse reduction in knockdown
efficiency relative to PEI alone. Mannosylation of the PEI-PEG could
be carried out without any significant reduction in knockdown
efficiency relative to PEI alone.
Kim
et al.
105
Further, chitosan is effective when
used as
carrier of siRNA and can mediate gene
silencing activity with no toxicity. Through complementary siRNA
technique and using chitosan, harmful genes can be “silenced” by
delivering it to target cells. Aigner has discussed in detail non-viral
strategies, based on different siRNA formulations and various modes
of administration, for the delivery of therapeutic siRNAs
in vitro
and
in vivo
106
in vivo
.
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