Efficient colonic delivery of DsiRNA by Pectin-Coated polyelectrolyte complex nanoparticles

Preparation, characterization and improved gastric survivability

Zahid Hussain, Haliza Katas, Set Li Yan, Diyanadalila Jamaludin

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1016-1027
Number of pages12
JournalCurrent Drug Delivery
Volume14
Issue number7
DOIs
Publication statusPublished - 1 Jan 2017

Fingerprint

Nanoparticles
Small Interfering RNA
Stomach
Chitosan
Water
Colorectal Neoplasms
Colon
Polyelectrolytes
pectin
Particle Size
Adenocarcinoma
Electrons
Gene Expression

Keywords

  • Complexation
  • DsiRNA
  • Efficient colonic delivery
  • Improved pharmaceutical performance
  • Pectin-coating
  • Water-soluble chitosan

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Efficient colonic delivery of DsiRNA by Pectin-Coated polyelectrolyte complex nanoparticles : Preparation, characterization and improved gastric survivability. / Hussain, Zahid; Katas, Haliza; Yan, Set Li; Jamaludin, Diyanadalila.

In: Current Drug Delivery, Vol. 14, No. 7, 01.01.2017, p. 1016-1027.

Research output: Contribution to journalArticle

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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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AB - 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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