Multiscale Co-reconstruction of Lung Architectures and Inhalable Materials Spatial Distribution

Abstract

The effective pulmonary deposition of inhaled particulate carriers loaded with drugs is a prerequisite for therapeutic effects of drug delivery via inhalation route. Revealing the sophisticated lung scaffold and intrapulmonary distribution of particles at three-dimensional (3D), in-situ, and single-particle level remains a fundamental and critical challenge for dry powder inhalation in pre-clinical research. Here, taking advantage of the micro optical sectioning tomography system, the high-precision cross-scale visualization of entire lung anatomy is obtained. Then, co-localized lung-wide datasets of both cyto-architectures and fluorescent particles are collected at full scale with the resolution down to individual particles. The precise spatial distribution pattern reveals the region-specific distribution and structure-associated deposition of the inhalable particles in lungs, which is undetected by previous methods. Overall, this research delivers comprehensive and high-resolution 3D detection of pulmonary drug delivery vectors and provides a novel strategy to evaluate materials distribution for drug delivery.