Determinants of drug and polypeptide bioavailability from aerosols delivered to the lung

Inhalation offers some exciting possibilities for the delivery of new generation products of biotechnology like polypeptides and proteins. Although the lungs and respiratory tract can metabolize some fraction of a delivered dose, the route offers an enormous absorptive surface area capable of delivering even large compounds to the circulation at acceptable rates. Dosimetry problems which are commonly associated with the administration of inhalation aerosols are inapplicable when lung-normal patients are considered. However, the dependence of lung metabolism and absorption upon molecular structure is poorly understood and requires further research. In the near future, it is likely that optimal formulations will be combined with modified aerosol delivery devices to maximize and achieve reproducible values for dose to lung. These will be used as alternatives to parenteral delivery for small through intermediate dose drugs which are not absorbed via the gastro-intestinal tract. Aerosol formulation, dosing and stability issues are discussed for proteins and other macromolecules, alongside the factors which are known to control and enhance pulmonary absorption. Issues concerning local immune responses are discussed especially as they may limit macromolecule delivery via inhalation.