Drug Discovery Today: technologies, Vol. 2, 2005, 39-46

Performance-driven, pulmonary delivery of systematically acting durgs

Rita Vanbever, Université catholique de Louvain, School of Pharmacy, Brussels, Belgium

Systemic drug delivery using inhalation aerosols presents requirements and challenges. To be well absorbed from the lung, a compound needs to be delivered to the alveolar region and recent high technology inhaler systems have allowed increased efficiency of drug administration to the deep lung. Yet, clearance mechanisms within the respiratory tissue operate effectively and considerably diminish bioavailabilities. Methods for enhancing drug absorption from the lung have been investigated. Viable and recent strategies to accelarate drug transport across respiratory epithelia or to decrease the rate of local degradation processes are reported.

Inhalation aerosols have ben used for therapy of lung pathologies for thousands of years but have been developed for systemic therapeutic applications only since the 1990s. This recent interest in systemic absorption from the lung results from the increasing number of drugs with a proteinous nature, the quest for their noninvasive administration as well as the recent comprehensive understanding of particle deposition within the respiratory system.

The first challenge in systemic delivery by inhalation has been to deliver with high efficiency and reliability the aerosol dose to the alveoli, the optimal site for systemic drug absorption. This challenge has been succesfully overcome. THis review aims at underlying parameters of the drug (e.g. biological stability within the pulmonary tissue) and lung (anatomo-physiology of the airways and alveoli) that affect systemic absorption. It aims at showing that clearance mechanisms within the lung compete with drug transport from the lung lumen to the bloodstream and at proposing viable strategies to overcome degradation pathways and to further increase the efficiency of systemic delivery by inhalation.