Zahid Hussain, Haliza Katas*, Set Li Yan and Diyanadalila Jamaludin Pages 1016 - 1027 ( 12 )
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.
Complexation, DsiRNA, efficient colonic delivery, improved pharmaceutical performance, pectin-coating, watersoluble chitosan.
Department of Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam 42300, Selangor, Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300