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The design of particles with enhanced aerodynamic properties can improve lung distribution and deposition, and hence the efficacy of encapsulated inhaled drugs. This study describes the nanoengineering and nebulization of metal\u2013phenolic capsules as pulmonary carriers of small molecule drugs and macromolecular drugs in lung cell lines, a human lung model, and mice. Tuning the aerodynamic diameter by increasing the capsule shell thickness (from \u2248100 to 200 nm in increments of \u224850 nm) through repeated film deposition on a sacrificial template allows precise control of capsule deposition in a human lung model, corresponding to a shift from the alveolar region to the bronchi as aerodynamic diameter increases. The capsules are biocompatible and biodegradable, as assessed following intratracheal administration in mice, showing &gt;85% of the capsules in the lung after 20 h, but &lt;4% remaining after 30 days without causing lung inflammation or toxicity. Single\u2010cell analysis from lung digests using mass cytometry shows association primarily with alveolar macrophages, with &gt;90% of capsules remaining nonassociated with cells. The amenability to nebulization, capacity for loading, tunable aerodynamic properties, high biocompatibility, and biodegradability make these capsules attractive for controlled pulmonary delivery.<\/jats:p>","DOI":"10.1002\/advs.201902650","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T13:33:05Z","timestamp":1578663185000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Engineering of Nebulized Metal\u2013Phenolic Capsules for Controlled Pulmonary Deposition"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0103-1207","authenticated-orcid":false,"given":"Yi","family":"Ju","sequence":"first","affiliation":[{"name":"ARC Centre of Excellence in Convergent Bio\u2010Nano Science and Technology, and the Department of Chemical Engineering The University of Melbourne  Parkville Victoria 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5341-175X","authenticated-orcid":false,"given":"Christina","family":"Cortez\u2010Jugo","sequence":"additional","affiliation":[{"name":"ARC Centre of Excellence in Convergent Bio\u2010Nano Science and Technology, and the Department of Chemical Engineering The University of Melbourne  Parkville Victoria 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingqu","family":"Chen","sequence":"additional","affiliation":[{"name":"ARC Centre of Excellence in Convergent Bio\u2010Nano Science and Technology, and the Department of Chemical Engineering The University of Melbourne  Parkville Victoria 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7722-8087","authenticated-orcid":false,"given":"Ting\u2010Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Nanobiotechnology Laboratory Australian Centre for Blood Diseases Central Clinical School Monash University  Melbourne Victoria 3004 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4454-853X","authenticated-orcid":false,"given":"Andrew J.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Materials Characterisation and Fabrication Platform The University of Melbourne  Parkville Victoria 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Tsantikos","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathology Central Clinical School Monash University  Melbourne Victoria 3004 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2130-1377","authenticated-orcid":false,"given":"Nadja","family":"Bertleff\u2010Zieschang","sequence":"additional","affiliation":[{"name":"ARC Centre of Excellence in Convergent Bio\u2010Nano Science and Technology, and the Department of Chemical Engineering The University of Melbourne  Parkville Victoria 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Institute Department of Microbiology Monash University  Clayton Victoria 3800 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9215-4845","authenticated-orcid":false,"given":"Jiaying","family":"Song","sequence":"additional","affiliation":[{"name":"ARC Centre of Excellence in Convergent Bio\u2010Nano Science and Technology, and the Department of Chemical Engineering The University of Melbourne  Parkville Victoria 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhe","family":"Cheng","sequence":"additional","affiliation":[{"name":"ARC Centre of Excellence in Convergent Bio\u2010Nano Science and Technology, and the Department of Chemical Engineering The University of Melbourne  Parkville Victoria 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas","family":"Mettu","sequence":"additional","affiliation":[{"name":"School of Chemistry and the Department of Chemical Engineering The University of Melbourne  Parkville Victoria 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7994-2097","authenticated-orcid":false,"given":"Md. 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