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  • Title: Efficient Colonic Delivery of DsiRNA by Pectin-Coated Polyelectrolyte Complex Nanoparticles: Preparation, Characterization and Improved Gastric Survivability.
    Author: Hussain Z, Katas H, Yan SL, Jamaludin D.
    Journal: Curr Drug Deliv; 2017; 14(7):1016-1027. PubMed ID: 28240178.
    Abstract:
    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.
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