Abstract
Recently, Dicer-substrate small interfering RNA (DsiRNA) has gained attention owing to its greater potency over small interfering RNA (siRNA). However, the use of DsiRNA is restricted by its rapid degradationin vitro. To address this issue, chitosan nanoparticulate deliver yplatform for the Dicer-substrate siRNA (DsiRNA) was developed and characterized. Nanoparticles were prepared by simple complexation and ionic gelation methods. The mean particle size of DsiRNA-adsorbed chitosan nanospheres (DsiRNA-CS NPs) prepared by the ionic gelation method ranged from 225 to 335 nm, while simple complexation yielded DsiRNA-chitosan complexes (DsiRNA-CS complexes) ranging from 270 to 730 nm. The zeta potential of both types of nanoparticles ranged from +40 to +65 mV. TEM and AFM micrographs revealed spherical and irregular morphology of DsiRNA-CS NPs and DsiRNA-CS complexes. ATR-FTIR spectroscopy confirmed the presence of DsiRNA in the CS NPs/complexes. Both types of nanoparticles exhibited sustained release and high binding and encapsulation (100%) efficiency of DsiRNA. DsiRNA-CS NPs/complexes showed low, concentration-dependent cytotoxicityin vitro. DsiRNA-CS NPs showed better stability than the complexes when stored at 4 and 25°C. Thus, it is anticipated that CS NPs are promising vectors for DsiRNA delivery due to their stability, safety, and cost-effectiveness.
Highlights
Successful gene delivery and expression remain a major difficulty that must be overcome before genetic therapies gain clinical acceptance
FTIR spectra confirmed the successful preparation of the CS nanospheres (CS NPs), DsiRNACS NPs and Dicer-substrate small interfering RNA (siRNA) (DsiRNA)-CS complexes
The results showed that DsiRNA-CS NPs remained more stable at different polymeric concentrations, resulting in spherical morphology, at different CS concentrations
Summary
Successful gene delivery and expression remain a major difficulty that must be overcome before genetic therapies gain clinical acceptance. Charged cationic polymers can effectively bind to and protect nucleic acids such as DNA, oligonucleotides, and siRNAs. Nonviral delivery systems using cationic liposomes and polymers, such as polyethylenimine (PEI), poly(L-lysine) (PLL), and their respective derivatives, have been used to condense plasmid DNA (pDNA) or siRNA to form nanoparticles [4,5,6]. Low molecular weight (LMW) CS nanoparticles have shown great potential in the applications of drug delivery and nonviral vector for gene delivery. This is because, compared with high molecular weight (HMW) chitosan, LMW chitosan shows better solubility, biocompatibility, bioactivity, biodegradability, and even less toxicity [18]. The efficiency of DsiRNA encapsulation, binding, and storage stability was studied
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