Pharmacokinetics and pharmacodynamics of RNA nanoparticles

Nanotechnology holds promise for optimizing or improving the delivery of a variety of active pharmaceutical ingredients intended for therapeutic purposes (Peer et al. 2007). In most cases, nanoformulations are chosen as a way to alter the pharmacokinetics and biodistribution of the active ingredient in an attempt to improve its pharmacodynamic effect and attenuate or alleviate potential toxicities (Drummond et al. 2008; Li and Huang 2008). Nanoformulations have also been considered as a means to deliver nucleic acid-based constructs; given that the latter have marginal stability in physiological fluids (Huang et al. 2010). More recently, however, RNA constructs have been designed with high plasma stability, and the need for encapsulation in nanoformulations is likely to be obviated (Guo 2010; Guo et al. 2010; Shu et al. 2011a). Regardless of this RNA-specific advance, the physical properties of particles as well as their interaction with plasma constituents dictates, to a large extent, their mode of clearance (Drummond et al. 2008). Here, we will briefly outline these factors and summarize the existing pharmacokinetic data for RNA nanoparticles, which, not surprisingly, is sparse.