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

✍ Scribed by Xiudong Liu; Kenneth A. Howard; Mingdong Dong; Morten Ø. Andersen; Ulrik L. Rahbek; Mads G. Johnsen; Ole C. Hansen; Flemming Besenbacher; Jørgen Kjems

• Publisher: Elsevier Science
• Year: 2007
• Tongue: English
• Weight: 437 KB
• Volume: 28
• Category: Article
• ISSN: 0142-9612
• DOI: 10.1016/j.biomaterials.2006.11.004

✦ Synopsis

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 (M w ) and degree of deacetylation (DD). High M w and DD chitosan resulted in the formation of discrete stable nanoparticles $200 nm in size. Chitosan/siRNA formulations (N:P 50) prepared with low M w ($10 kDa) showed almost no knockdown of endogenous enhanced green fluorescent protein (EGFP) in H1299 human lung carcinoma cells, whereas those prepared from higher M w (64.8-170 kDa) and DD ($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 M w (114 and 170 kDa) and DD (84%) that correlated with formation of stable nanoparticles of $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.