The years since the early 1990s have seen many new scientific and engineering developments related to the therapeutic inhalation technology, especially for systemic delivery of drugs to the lungs. From novel inhaler to novel particle design [1], these developments have focused largely on improving the efficiency of the delivery of inhaled drugs to the lungs while limiting inhaler system user complexity. In the most successful delivery systems, lung deposition efficiencies, measured relative to the nominal dose of drug in the inhaler, have increased from approximately 10% to 60% [1], and delivery reproducibility has improved as well. Nevertheless, while early reports of inhaled insulin biovailability in animals suggested numbers as high as 50% [2] and sustained pharmacodynamic action following deposition in the lungs of several days [3], published results from the most advanced human insulin trials [4] show relative biopotencies of less than 5%, and no public data have yet emerged from the clinic to confirm the feasibility of long-acting insulin delivery through the lungs. These circumstances point to the need for continued scientific and technological innovation if inhaled delivery of drugs for systemic application is to achieve widespread commercial use.

This chapter focuses on two recently published studies in the Proceedings of the National Academy of Sciences [5,6] related to inhalation delivery systems for the treatment of diseases modulated by the systemic circulation. We attempt to critically examine the results in the context of current technology and discuss their implications on the challenges facing the inhalation drug delivery field today.

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