Abstract
Pulmonary disease has been the primary target of inhaled therapeutics for over 50 years. During that period, increasing interest has arisen in the use of this route of administration to gain access to the systemic circulation for the treatment of a number of diseases beyond the airways. In order to effectively employ this route, the barriers to transport from the lungs following deposition of aerosols must be considered, including the nature of the disease (whether proximal, as in pulmonary hypertension, or distal, as in diabetes). Delivery to the systemic circulation begins with the efficiency of aerosol generation and subsequent deposition in the airways and proceeds to the influence of mechanisms of clearance, including absorption, metabolism, and mucociliary and cell-mediated transport, on the residence time of the drugs in the lungs. The nature of the drug (small or large molecules/low or high molecular weight), susceptibility to degradation and general physicochemical properties play a role in the chemistry of its formulation, physics of aerosol delivery and biology of disposition.