Future Directions For Aerosol

In general, drugs currently administered as aerosols are used principally for the treatment of pulmonary disorders. This line of thinking centers on providing a high local concentration while diminishing systemic absorption and associated side effects. Current research emphasizes this doctrine, examples of which are the development of longer-acting bronchodilator drugs by hindering absorption through molecular modifications (e.g., salmeterol, formoterol) [29] or incorporation into liposomes [147]. What then lies in the future for aerosols in pharmacology, other than the treatment of obstructive airways disease? The potential of aerosols as a means of delivering drugs to the pulmonary and systemic circulations is now starting to be explored and it represents a valuable direction for future research. The rapid onset of action and circumvention of firstpass hepatic metabolism favor the airways as a site of drug disposition for systemic activity. With continuing advancements being made in recombinant DNA technology, therapeutic entities of the future will undoubtedly comprise peptides and proteins. These agents are currently administered via the subcutaneous, intramuscular, or intravenous routes, which lead to poor compliance by patients and necessitate greater health care professional involvement. As a result, alternative routes that are more "patient friendly" are being examined, such as intranasal and aerosol inhalation. The development and success (or failure) of inhaled insulin as a therapeutic entity will serve as an important yardstick for the future of inhaled proteins. The efficiency of delivery and retention in the lung of a significant portion of a total dose of an aerosol are critical for the inhalation route of administration to be useful, particularly when using expensive recombinant products. Introduction of the use of spacer devices with metered-dose inhalers may advance the cause of aerosols by increasing the amount of aerosol introduced into the airways (making the therapy more effective) and decreasing the amount depositing in the mouth (and thereby diminishing side effects associated with oral or gastrointestinal absorption).

These considerations notwithstanding, the extent to which the airways can be used as a site of drug delivery to the systemic circulation remains to be fully defined. Although a considerable amount is known about the manner in which airway caliber and mucus secretion are influenced by pharmacological agents, relatively little is understood about the pharmacokinetic effect of drugs delivered to the lumen of the central and peripheral airways. What happens to a drug in passage from the lumen to its therapeutic target tissue (be it airway, smooth muscle, or blood)? In the development of an aerosolized drug for therapeutic use, the overriding emphasis lies in its capacity to produce a therapeutic or biological response. Perhaps if more were known about the pharmacokinetic processes of the airways, biologically active drugs that are inactive as an aerosol may be structurally modified to resist absorptive or metabolic pressures and thereby establish a therapeutic entity.

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