Pulmonary delivery of locally-acting drugs encapsulated in nanocarriers provides several advantages for the
treatment of respiratory diseases such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis, tuberculosis and
lung cancer. These advantages include, among others, sustained drug delivery to the lungs, reduced therapeutic dose and
improved patient compliance. The aim of this review is to give an updated overview on recent advances recorded in the
last few years in this field as well as on the major challenges still existing and that remain to be overcome before any
clinical application. After an outline on the cellular and extracellular barriers affecting drug delivery to the airways both in
physiological and pathological conditions, the significant developments recorded using inhaled polymeric- and lipid-based
nanocarriers for drug and gene delivery to the lung are presented. In this discussion, the major challenges existing in the
field are evidenced including the understanding of the factors governing the mucus penetration capability of these nanocarriers
and the identification of new technologies for delivering drugs to specific regions or cell types of the lungs. In this
regard, the recognition of receptor expressed only at lung level may facilitate drug targeting to this organ and it should
improve the therapeutic efficacy of nanocarrier-based treatments for respiratory diseases.
Keywords: Defense mechanisms, inhalation of polymeric- and lipid-based nanocarriers, lung targeting, mucus penetration,
pulmonary delivery, respiratory diseases.
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