ABSTRACT
Systemic, intravenous, delivery has been the most widely investigated delivery route thus far due to the ease of administration as well as the rapid distribution to various tissue sites. However, it has historically been considered the most complex route of delivery, due to the size, charge, instability, and short half-life of injected siRNAs. This short half-life is caused by renal clearance and endogenous ribonuclease digestion [2]. These obstacles can be reduced by incorporating siRNAs into particles and complexes or by chemically modifying the RNA backbone. The chemical modification of the siRNA backbone through introduction of phosphorothioate and 2′-O-methyl sugar residues shows enhanced resistance toward degradation by exoand endonucleases in serum and tissue [3]. However, even modified, naked siRNAs have poor cellular uptake due to their small size, net negative charge, renal clearance, and hydrophilicity [4]. Therefore a range of delivery vectors such as liposomes, polymers, and nanoparticles have been developed to facilitate cellular absorption as well as provide a degree of protection and increase systemic circulation time.
