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Updated: Mar 7, 2026
Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
Published on: May 2, 2019
Efficient Colonic Delivery of DsiRNA by Pectin-Coated Polyelectrolyte Complex Nanoparticles: Preparation,
Zahid Hussain1, Haliza Katas2, Set Li Yan2
1Department of Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam 42300, Selangor. Malaysia.
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.
Insights
Water-soluble chitosan nanoparticles carrying Dicer-substrate small interfering RNA (DsiRNA) show promise for colorectal cancer treatment. These nanoparticles protect DsiRNA from degradation and enable targeted delivery to the colon.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Therapy
Background:
- Dicer-substrate small interfering RNA (DsiRNA) exhibits potent anticancer effects but faces challenges in cellular uptake and stability.
- Poor delivery hinders the therapeutic application of DsiRNA for colorectal cancer.
Purpose of the Study:
- To develop a novel delivery system for DsiRNA to overcome pharmaceutical limitations.
- To enhance DsiRNA delivery to the colon for effective colorectal cancer treatment.
Main Methods:
- Preparation of water-soluble chitosan (WSC)-DsiRNA complex nanoparticles (NPs).
- Coating NPs with pectin to protect DsiRNA from the gastric environment.
- Characterization of NP size, zeta potential, and morphology.
- Evaluation of cytotoxicity and DsiRNA release profiles in simulated physiological fluids.
Main Results:
- WSC-DsiRNA NPs exhibited variable sizes (145-867 nm) and zeta potentials (+38 to -6.2 mV) depending on WSC and pectin concentrations.
- Electron microscopy showed spherical to irregular morphologies.
- DsiRNA demonstrated dose-dependent cytotoxicity against colorectal adenocarcinoma cells.
- Low DsiRNA release in gastric/intestinal fluids (<15%/30%) and high release in colonic fluid (>90%) confirmed suitability for colonic delivery.
Conclusions:
- WSC-DsiRNA complexes show significant potential as a carrier system for colon-specific DsiRNA delivery.
- This approach offers a promising strategy for the targeted treatment of colorectal cancer.
