Pulmonary delivery: innovative approaches and perspectives

The respiratory system, as well as the skin, are organs in direct contact with the environment and they represent pos- sible doors for the entrance of therapeutic agents into the body. Because of the increasing incidence of pulmonary dis- eases with high mortality and morbidity, pulmonary drug delivery is emerging as a non-invasive and attractive ap- proach for the treatment of several pathologies. It must be pointed out that the development of drug delivery systems for pulmonary application requires a detailed knowledge of the lung, both in its healthy and disease state. Among the vari- ous drug delivery systems considered for pulmonary application, nanocarriers show several advantages over other conventional approaches for the treatment of respiratory diseases, for example prolonged drug release and cell-specific targeted drug delivery. Nano-size drug carriers can incorporate various therapeutics (e.g., poorly water soluble drugs, macromolecules) and show interesting features as drug delivery systems to the lung, such as: controlled release, pro- tection from metabolism and degradation, decreased drug toxicity and targeting capabilities. Since gene therapy (e.g. small interfering RNA, siRNA) is currently being developed for a wide range of acute and chronic lung diseases, in- cluding CF, cancer and asthma, the use of nanocarriers for lung release/targeting represents a promising application of such nano-sized structures. Despite the many promising proof of concepts of various delivery technologies reported in this review, further efforts are needed to ensure the safety of long-term in vivo applications and the development of scale up from laboratory to industry in order to reach, together with safety, large-scale production at affordable costs of innovative lung delivery technologies.