The approval by the Food and Drug Administration (FDA) of the first inhaled insulin combination product for treatment of diabetes represents a milestone in drug delivery. Exubera is an inhaled powder form of recombinant human insulin (rDNA) used in the treatment of adult patients with type 1 and type 2 diabetes and is the first new delivery option introduced since the discovery of insulin in the 1920s. A new study published by a market research firm reports that 2006 revenues for the total pulmonary drug delivery market reached $25.5 billion, an increase of 11.8 per cent since 2002. Sales of drug delivery technologies alone increased from $1.4-1.6 billion during this four-year period. Similarly, pharmaceuticals delivered through pulmonary means grew to $23.9 billion, with the overall market showing a compound annual growth rate of nearly 10 per cent during this time period. Non-respiratory therapies will comprise a significant portion of the expanding number of drugs administered via this route.

THE TREE OF LIFE

The respiratory system has often been likened to a tree with the trachea serving as the trunk, bronchi as the branches and the alveoli serving as the leaves. The trachea divides to form two bronchi and the two forks lead to the individual lung lobes. Within the lobes, the bronchi further divide to form new generations of smaller airways known as the bronchioles. These airways are a series of passages and further divide to produce 25 generations that terminate in the alveolar sacs. All the airways narrow toward the alveoli, and drugs administered via this route enter the bloodstream accordingly. The alveolar surface of the lungs is made up of bronchioles, alveolar ducts and alveoli and accounts for more than 95 per cent of the absorptive area of the pulmonary system. This area is lined by a very thin vesiculated and richly perfused monolayer of epithelial cells. The unique cellular properties of the airway epithelium offer great potential for drug delivery. Among the different respiratory cells, the ciliated epithelial cells of the larger and smaller airways and the type 1 and 2 pneumocytes are the key to pulmonary drug transport.

Due to their diverse cellular characteristics, each of these cell types provides unique potential for absorption of the compound. In addition, the immunotolerant nature of the lung is beneficial from a tolerance perspective. Although all protocols for inhalation toxicology share similar characteristics, the knowledge and expertise required to correctly design and conduct studies for pharmaceutical compounds pose special challenges.