Carrier interactions with the biological barriers of the lung: Advanced in vitro models and challenges for pulmonary drug delivery

In recent years significant progress has been made to improve particle deposition in the lung. However, the development of strategies to overcome the air–blood lung barrier is still needed. The combination of complex in vitro models and sophisticated particulate carriers is promising as a strategy by which that goal could be achieved. In this review we discuss currently available in vitro lung models, including some recent tissue-engineering approaches, as well as the challenges associated to implement such complex in vitro systems. Furthermore, we discuss available carrier technologies, often based on nanotechnology, to target specific regions of the lungs and to overcome the respective biological barriers, ideally resulting in safe and effective delivery to the desired pulmonary destination.