Open AccessEngineering of Nebulized Metal–Phenolic Capsules for Controlled Pulmonary Deposition
Author(s) -
Ju Yi,
CortezJugo Christina,
Chen Jingqu,
Wang TingYi,
Mitchell Andrew J.,
Tsantikos Evelyn,
BertleffZieschang Nadja,
Lin YuWei,
Song Jiaying,
Cheng Yizhe,
Mettu Srinivas,
Rahim Md. Arifur,
Pan Shuaijun,
Yun Gyeongwon,
Hibbs Margaret L.,
Yeo Leslie Y.,
Hagemeyer Christoph E.,
Caruso Frank
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201902650
Subject(s) - capsule , lung , biocompatibility , aerodynamic diameter , nanoengineering , pulmonary surfactant , materials science , biomedical engineering , chemistry , nanotechnology , medicine , aerosol , organic chemistry , biochemistry , botany , metallurgy , biology
Particle‐based pulmonary delivery has great potential for delivering inhalable therapeutics for local or systemic applications. 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–phenolic 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 ≈100 to 200 nm in increments of ≈50 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 >85% of the capsules in the lung after 20 h, but <4% remaining after 30 days without causing lung inflammation or toxicity. Single‐cell analysis from lung digests using mass cytometry shows association primarily with alveolar macrophages, with >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.