the basic pathophysiological processes that lead to this complication should make it

possible to devise optimal therapies for individual patients suffering from neuro-

pathic pain (Tölle 2010).

20.3

siRNA Nanocarrier as Plausible Therapeutic Recourse

20.3.1 siRNA

The discovery of siRNA in 1999 was guided by the sequence-influenced endonucle-

ase-based cleavage of mRNA in mammal cells. Further, in 2001, synthesized siRNA

was utilized for silencing. Henceforth, the principle and structure of siRNA were

elucidated, which paved a way for future implications of RNAi in therapeutics (Dana

et al. 2017). RNA interference is a natural process occurring in multicellular

organisms involving the silencing of genes. The complementary RNA is degraded

in this post-transcription event originating through the double-stranded RNA.

siRNA possesses merely 21 nucleotide sequences which are utilized as a tool for

gene silencing specifically in mammal cells facilitating specificity of interferon

activity (Kurreck 2006). siRNA offers an innovative recourse to the available

therapeutic alternatives. They offer a safer option as they act on the post-translational

stages of DNA expression. As a result, they do not influence the genetic material

directly and hence evading mutagenic risks. With its impactful efficacy, siRNA

causes potent suppression of gene expression with the use of one cell and associated

few copies. Another advantage is offered by the specificity of complementary bases

as compared to chemical therapeutics. However, many limitations are presented in

the delivery of siRNA to the targeted cell site. siRNA is very unstable under normal

physiology in the blood wherein it undergoes digestion by nuclease enzymes

(Subhan and Torchilin 2019). Thus, the development of drug delivery systems that

can enhance site-specific delivery of siRNA therapeutics for aiding relief from

disease is required.

20.3.2 siRNA Nanocarrier as Drug Delivery System

siRNA are prone to degradation by nucleases and require attention to protect it

from blood enzymes. Transfection agents are needed to facilitate their movement

across the membrane since siRNA possesses an overall negative charge (Zhang et al.

2018). Efficient nanocarriers should ensure evasion from immunogenic recognition

and clearance through our reticuloendothelial system. Serum proteins like albumin

and IgG tend to interact with siRNA cationic bodies, leading to the enhanced size of

the complex. This ultimately lessens the targeted siRNA fraction that reaches the

target site (Meng et al. 2013). Attaching a ligand entity like an antibody, aptamer, or

peptide provides specificity to the siRNA molecule and ensures release at the desired

site of action. Lipid nanoparticles possessing a positive charge attributed through

cation lipidic formulations are efficient in condensing the genes and ensuring uptake

20

siRNA-Encapsulated Nanoparticles for Targeting Dorsal Root Ganglion (DRG). . .

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