Chitosan-based nanoparticles for in vivo delivery of interfering agents including siRNA

The potential of siRNA to knock down expression of genes has been identified as an exciting strategy for specific treatments of disease-associated genes. However, their clinical development is pended to the achievement of their effective intracellular delivery in the target cells in vivo. So far, this was a bottleneck for fast development of siRNA in clinics because of their high enzymatic susceptibility in biological media and their poor intracellular uptake. The realization of therapeutic potential of the RNA interference approach strongly depended on the rational design of safe and effective carriers. This review considers carriers made of chitosan-based nanoparticles. It reports the methods of synthesis and the interactions of siRNA with chitosan which is at the basis of the association, stability and delivery to cells of siRNA with these carriers. Results of evaluations of the interference activity produced in vitro and in vivo by the interfering molecule delivered with chitosan-based nanoparticle carriers are discussed. As pointed out from different examples, the remarkable efficacy of the chitosan-based nanoparticles to deliver active interfering agents in vivo and to achieve a successful systemic delivery including by oral administration are very encouraging. Although we are still in the early stage of developments, it can be expected that results reported so far paved the road to stimulate further developments and strengthen their clinical application perspectives.