State-of-the-Art Review on Inhalable Lipid and Polymer Nanocarriers: Design and Development Perspectives.

Nowadays, the interest in research towards the local administration of drugs via the inhalation route is growing as it enables the direct targeting of the lung tissue, at the same time reducing systemic side effects. This is of great significance in the era of nucleic acid therapeutics and personalized medicine for the local treatment of severe lung diseases. However, the success of any inhalation therapy is driven by a delicate interplay of factors, such as the physiochemical profile of the payload, formulation, inhalation device, aerodynamic properties, and interaction with the lung fluids. The development of drug delivery systems tailored to the needs of this administration route is central to its success and to revolutionize the treatment of respiratory diseases. With this review, we aim to provide an up-to-date overview of advances in the development of nanoparticulate carriers for drug delivery to the lung tissue, with special regard concerning lipid and polymer-based nanocarriers (NCs). Starting from the biological barriers that the anatomical structure of the lung imposes, and that need to be overcome, the current strategies to achieve efficient lung delivery and the best support for the success of NCs for inhalation are highlighted.

Rational particle design to overcome pulmonary barriers for obstructive lung diseases therapy.

Pulmonary delivery of active drugs has been applied for the treatment of obstructive lung diseases, including asthma, chronic obstructive pulmonary disease and cystic fibrosis, for several decades and has achieved progress in symptom management by bronchodilator inhalation. However, substantial progress in anti-inflammation, prevention of airway remodeling and disease progression is limited, since the majority of the formulation strategies focus only on particle deposition, which is insufficient for pulmonary delivery of the drugs. The lack of knowledge on lung absorption barriers in obstructive lung diseases and on pathogenesis impedes the development of functional formulations by rational design. In this review, we describe the physiological structure and biological functions of the barriers in various regions of the lung, review the pathogenesis and functional changes of barriers in obstructive lung diseases, and examine the interaction of these barriers with particles to influence drug delivery efficiency. Subsequently, we review rational particle design for overcoming lung barriers based on excipients selection, particle size and surface properties, release properties and targeting ability. Additionally, useful particle fabrication strategies and commonly used drug carriers for pulmonary delivery in obstructive lung diseases are proposed in this article.