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Certain pulmonary diseases, such as cystic fibrosis (CF), non-CF bronchiectasis, chronic obstructive pulmonary disease, and ventilator-associated pneumonia, are usually accompanied by respiratory tract infections due to the physiological alteration of the lung immunological defenses. Recurrent infections may lead to chronic infection through the formation of biofilms. Chronic biofilm-based infections are challenging to treat using antimicrobial agents. Therefore, effective ways to eradicate biofilms and thus relieve respiratory tract infection require the development of efficacious agents for biofilm destruction, the design of delivery carriers with biofilm-targeting and/or penetrating abilities for these agents, and the direct delivery of them into the lung. This review provides an in-depth description of biofilm-based infections caused by pulmonary diseases and focuses on current existing agents that are administered by inhalation into the lung to treat biofilm, which include i) inhalable antimicrobial agents and their combinations, ii) non-antimicrobial adjuvants such as matrix-targeting enzymes, mannitol, glutathione, cyclosporin A, and iii) liposomal formulations of anti-biofilm agents. Finally, novel agents that have shown promise against pulmonary biofilms as well as traditional and new devices for pulmonary delivery of anti-biofilm agents into the lung are also discussed.

Lipid nanoparticles are increasingly used for drug and gene delivery, including the delivery of small interfering RNA (siRNA). Pulmonary delivery of drug molecules carried by lipid nanoparticles directly into the lung may improve the treatment of certain lung diseases. The present study was designed to test the feasibility of engineering aerosolizable dry powder of lipid nanoparticles by thin-film freeze-drying (TFFD). Solid lipid nanoparticles (SLNs) comprised of lecithin, cholesterol, and a lipid-polyethylene glycol conjugate were prepared by solvent evaporation. Dry powders of the SLNs were prepared by TFFD, spray drying, or conventional shelf freeze-drying. The physical and aerosol properties of the dry powders as well as the physical properties of the SLNs reconstituted from the dry powders were evaluated. The particle size, polydispersity index, and the zeta potential of the SLNs were preserved after they were subjected to TFFD and reconstitution, but not after they were subjected to conventional shelf freeze-drying and reconstitution, and the dry powder prepared by TFFD showed better aerosol performance properties than that prepared by spray drying. SLNs encapsulated with siRNA can also be successfully transformed into aerosolizable dry powder by TFFD, and subjecting the siRNA-encapsulated SLNs to TFFD did not negatively affect the function of the siRNA. It is concluded that TFFD represents a promising method to prepare aerosolizable dry powder of lipid nanoparticles.