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Review

Pulmonary Absorption of Peptides and Proteins

Pages 1-20 | Received 19 May 1994, Published online: 27 Sep 2008
 

Abstract

Pulmonary delivery provides a promising route for absorption of peptides and proteins having poor oral bioavailability due to inefficient transport across the gastrointestinal epithelium or high levels of first-pass hepatic clearance. Efficient absorption after inhalation has been demonstrated for compounds varying substantially in size and other physicochemical characteristics. However, understanding of the relationship of structure to absorption efficiency is incomplete. Limited data regarding mechanisms of permeation across respiratory epithelium suggest passive transport of small peptides, with a contribution from vesicle-mediated transcytosis in the relatively slow transport of large proteins such as albumin and peroxidase. Lack of absorption of some peptides is most likely due to their susceptibility to protease degradation, since high levels of some exopeptidases are present in lung tissue. Effects of chronic exposure to potentially antigenic molecules delivered to the lung will need to be assessed on a case by case basis before the potential for pulmonary peptide delivery can be determined. Formulation/device development for proteins is in early stages: the susceptibility of many proteins to denaturation and oxidation presents special difficulties in small particle aerosol generation. The relative inefficiency and volume limitations of inhalation delivery currently limit this approach to molecules of relatively high potency. More widespread exploitation of pulmonary polypeptide delivery will depend on successful development of reproducible dry powder systems allowing inhalation of a greater amount of drug.

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