Safety of inhaled proteins for therapeutic use

The use of the inhalation route for delivery of inhaled proteins has received increasing attention recently. The purpose of this article is to review the available information related to the safety aspects of inhaled proteins. The review focuses primarily on possible toxicity to the respiratory tract, because usually one is either considering an agent to treat the lung or an agent for which the systemic toxicity has been investigated following subcutaneous (s.c.) administration in its clinical use as a therapeutic agent. Some background is provided on mechanisms of absorption and reasons why inhalation delivery is considered for many proteins. Available data are summarized from clinical trials of proteins and protein-like biomolecules, generally showing minimal, if any, adverse respiratory effects. The results of the animal toxicology studies that have been published are presented. In general, the observed lung toxicity has been relatively low, and it has been difficult to interpret in cases where the animal protein differs considerably from the human protein. Discussion is presented on the possibility of adverse immune reactions, suggesting that this is not likely to be any greater issue than it is for subcutaneously injected materials. Although the safety information is relatively sparse at present, the available data suggest that the inhalation route can be an attractive route to consider for many therapeutic proteins.