Synthesis and characterization of chitosan-based nanocarriers for siRNA release

Small interfering RNA (siRNA) has been widely investigated due to its potential to treat diseases by the silencing of targeted genes1. However, the intracellular delivery of siRNAs molecules remains as an ongoing challenge due to their negative charges and susceptibility to degradation by endogenous enzymes. The development of nanosized carriers is a need to overcome the extra and intracellular barriers. Thus, chitosan derivatives containing tertiary amino groups and varied degrees of acetylation were synthesized and characterized by gel permeation chromatography (GPC) and 1H-NMR techniques. The complex coacervation process at varied charge ratios was employed to prepare nanoparticles with siRNA-CCR2 and the interaction was studied by gel retardation assay, dynamic light scattering and FEG-SEM. The derivatives efficiently complexed the siRNA at low charge ratios and formed spherical particles of 150 nm in size with zeta potentials varying from +10 to +13 mV. Cell viability studies showed that the modifications resulted in derivatives of low cytotoxicity and that imparting a moderated amphiphatic character to chitosan is a promising way to condense siRNA into nanoparticles.