With recent advances in the field of RNAi-based therapeutics, it is possible to make any target gene 'druggable', at least in principle. The present review focuses on aspects critical for pulmonary delivery of formulations of nucleic acid-based drugs. The first part introduces the therapeutic potential of RNAi-based drugs for the treatment of lung diseases. Subsequently, we discuss opportunities for formulation-enabled pulmonary delivery of RNAi drugs in light of key physicochemical properties and physiological barriers. In the following section, an overview is included of methodologies for imparting inhalable characteristics to nucleic acid formulations. Finally, we review one of the bottlenecks in the early preclinical testing of inhalable nucleic acid-based formulations, in other words, devices suitable for pulmonary administration of powder-based formulations in rodents.
Keywords: RNA interference; aerodynamic properties; cationic lipids; dry powder formulations; lung diseases; nanoparticles; nucleic acids; preclinical testing; pulmonary delivery; spray drying.