Propellant-based inhalers for the non-invasive delivery of genes via oral inhalation

In this work we describe the development of a propellant-based, portable oral inhalation platform for the pulmonary delivery of genes. A core–shell strategy is utilized to efficiently disperse cationic-polymer-DNA nanoparticles in hydrofluoroalkane propellants, and to generate aerosols from the corresponding pressurized metered-dose inhaler formulations (pMDIs) that have excellent aerosol characteristics, suitable for deep lung deposition. The engineered polyplexes and core–shell structures were fully characterized, and their ability to transfect model lung alveolar epithelium cells in vitro was demonstrated. We also show that the propellant does not affect the biological activity of the plasmid DNA, and that the core–shell formulations have no in vitro cytotoxicity. The relevance of this work stems from the fact that pMDIs are the least expensive and most widely used portable oral inhalation devices, and are thus promising platforms for targeting genes to the lungs for the treatment of medically relevant diseases including asthma, cystic fibrosis, chronic obstructive pulmonary disease, and lung cancer.

Graphical abstractCore–shell particles loaded with chitosan (CS)–DNA polyplexes were successfully formulated in pressurized metered-dose inhalers, showing to be a promising platform for targeting genes to the lungs via oral inhalation.Figure optionsDownload full-size imageDownload as PowerPoint slide