Background: Despite having excellent anticancer efficacy and ability to knockdown gene
expression, the therapeutic feasibility of Dicer-substrate small interfering RNA (DsiRNA) is limited
due to its poor cellular uptake, chemical instability and rapid degradation in biological environments.
Objective: The present study was aimed to circumvent the pharmaceutical issues related to DsiRNA
delivery to colon for the treatment of colorectal cancer.
Method: In this study, we have prepared water-soluble chitosan (WSC)-DsiRNA complex nanoparticles
(NPs) by a simple complexation method and subsequently coated with pectin to protect DsiRNA
from gastric milieu.
Results: The mean particle size and zeta potential of the prepared WSC-DsiRNA complexes were varied
from 145 ± 4 nm to 867 ± 81 nm and +38 ± 4 to –6.2 ± 2.7 mV respectively, when the concentrations
of WSC (0.1%, 0.2% and 0.3% w/v) and pectin (0.1%, 0.2% and 0.25% w/v) were varied. The
electron microscopic analysis revealed that morphology of WSC-DsiRNA complexes was varied from
smooth spherical to irregular spherical. Cytotoxicity analysis demonstrated that viability of colorectal
adenocarcinoma cell was decreased when the dose of WSC-DsiRNA was increased over the incubation
from 24 to 48 h. A significantly low cumulative release of DsiRNA in simulated gastric (<15%) and
intestinal fluids (<30%) and a marked increase in its release (>90%) in simulated colonic fluid (SCF)
evidenced the feasibility and suitability of WSC-DsiRNA complexes for the colonic delivery.
Conclusion: These findings clearly indicated promising potential of WSC-DsiRNA complexes as a
carrier to delivery DsiRNA to colon for the treatment of colorectal cancer.