Delivery of RNAi Therapeutics to the Airways—From Bench to Bedside

Qiu, Yingshan; Lam, Jenny K. W.; Leung, Susan W. S.; Liang, Wanling

Human respiratory tract is divided into the conducting region (nasal cavity, pharynx, trachea, bronchi and bronchioles) and the respiratory region (respiratory bronchioles and alveoli). The former is the pathway for gases conduction whereas the latter is the site of gaseous exchange [14] . The extensive branched structure of the airways with varying length and diameter presents the primary hurdle in pulmonary drug delivery. The mechanisms of inhaled particle deposition in the lungs include inertial impaction, gravitational sedimentation, diffusion, interception and electrostatic precipitation [33] . As illustrated in Figure 3 , the first three mechanisms are the major mechanisms which are greatly influenced by the aerodynamic size of the particles [34] . The optimal particle size for lung deposition is between 1 and 5 µm [35, 36] . Larger particles are likely to be impacted and trapped on the upper airway wall at bifurcations while the small particles from 0.1 to 1 µm are easily exhaled during normal breathing. Smaller particles under 100 nm may be successfully deposited in the alveolar space because of the increasing diffusional mobility [37] . However, aerosols under 100 nm are difficult to produce, which make their application less favorable.