The influence of polymeric properties on chitosan/siRNA nanoparticle formulation and gene silencing

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  • Department of Physics and Astronomy
  • Interdisciplinary Nanoscience Center
  • iNano-School
  • Department of Molecular Biology
  • Department of Molecular Biology
We have previously introduced the use of the biomaterial chitosan to form chitosan/siRNA nanoparticles for gene silencing protocols. This present study shows that the physicochemical properties (size, zeta potential, morphology and complex stability) and in vitro gene silencing of chitosan/siRNA nanoparticles are strongly dependent on chitosan molecular weight (Mw) and degree of deacetylation (DD). High Mw and DD chitosan resulted in the formation of discrete stable nanoparticles approximately 200 nm in size. Chitosan/siRNA formulations (N:P 50) prepared with low Mw (approximately 10 kDa) showed almost no knockdown of endogenous enhanced green fluorescent protein (EGFP) in H1299 human lung carcinoma cells, whereas those prepared from higher Mw (64.8-170 kDa) and DD (approximately 80%) showed greater gene silencing ranging between 45% and 65%. The highest gene silencing efficiency (80%) was achieved using chitosan/siRNA nanoparticles at N:P 150 using higher Mw (114 and 170 kDa) and DD (84%) that correlated with formation of stable nanoparticles of approximately 200 nm. In conclusion, this work confirms the application of chitosan as a non-viral carrier for siRNA and the importance of polymeric properties for the optimisation of gene silencing using chitosan/siRNA nanoparticles.
Original languageEnglish
JournalBiomaterials
Volume28
Issue6
Pages (from-to)1280-8
Number of pages8
ISSN0142-9612
DOIs
Publication statusPublished - 2007

    Research areas

  • Cell Line, Tumor, Chemistry, Pharmaceutical, Chitosan, Drug Carriers, Gene Silencing, Humans, Lung Neoplasms, Nanoparticles, Particle Size, RNA, Small Interfering

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