Controlled Drug Delivery via the Lung

Abstract

The lungs fulfill the vital function of transporting and exchanging breathing air. The respiratory tract is considered an excellent delivery route for local and noninvasive administration of active ingredients, even when its anatomy and physiology may represent an obstacle for drug delivery. For this reason, inhalable products are designed as complex systems composed by a drug formulation and an administration device (e.g. nebulizers, metered dose inhalers and dry powder inhalers).Traditionally, most inhalation aerosol products available are intended to treat respiratory diseases (e.g. asthma, cystic fibrosis, chronic obstructive pulmonary disease and allergic rhinitis). It should be highlighted that pulmonary administration avoids the hepatic first-pass metabolism. Recently, there has also been an increased interest to develop inhalable products for systemic administration, where the healthy lung is used as an access route for drugs, vaccines or proteins to the bloodstream. Several formulations, devices, and products have reached advanced development stages as well as regulatory approved therapeutics.In this context, controlled release strategies, based on spatial location and temporally modified delivery, have been used to optimize the pharmacotherapy. Approaches to: a) modify deposition in different tracheobronchial tree areas, b) protect the drugs from lung elimination mechanisms (e.g. mucociliar clearance and phagocytosis), c) sustain drug release and d) target to specific cells (such as macrophages) have been developed.This chapter presents the anatomical and physiological characteristics of the airways relevant to the design of drugs and the formulation and devices most used for controlled release.