title: Efficient Colonic Delivery of DsiRNA by Pectin-Coated Polyelectrolyte Complex Nanoparticles: Preparation, Characterization and Improved Gastric Survivability.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  These findings clearly indicated promising potential of WSC-DsiRNA complexes as a carrier to delivery DsiRNA to colon for the treatment of colorectal cancer.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam 42300, Selangor. Malaysia.
authors.forename: Zahid
authors.initials: Z
authors.lastname: Hussain
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300. Malaysia.
authors.forename: Haliza
authors.initials: H
authors.lastname: Katas
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300. Malaysia.
authors.forename: Set Li
authors.initials: SL
authors.lastname: Yan
authors.affiliation: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300. Malaysia.
authors.forename: Diyanadalila
authors.initials: D
authors.lastname: Jamaludin
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D003106:Colon / Q000378:metabolism*; D065546:Drug Liberation; D005750:Gastric Juice / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007419:Intestinal Secretions / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010368:Pectins / Q000008:administration & dosage* / Q000737:chemistry; D000071228:Polyelectrolytes / Q000008:administration & dosage* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000071228:Polyelectrolytes; D034741:RNA, Small Interfering; D010368:Pectins; D048271:Chitosan
keywords: Complexation; DsiRNA; efficient colonic delivery; improved pharmaceutical performance; pectin-coating; watersoluble
  chitosan