The deep lungs provide an efficient pathway for drugs to transport into the systemic circulation, as the
extremely large surface area and thin epithelial membrane enable rapid drug transport to the blood stream. To
penetrate into the deep lungs, aerosol particles with aerodynamic diameters of 1-3 m are optimal. Large porous
hollow particles (LPHPs) can achieve this aerodynamic size range through enhanced porosity within the particles
(typically < 0.4 g/cm3), which aerodynamically balances the large particle size (> 5 µm, up to 30 µm). The physical
properties of these particles provide some key advantages compared to their small, nonporous counterparts through
enhanced dispersibility, efficient deep lung deposition, and avoidance of phagocytic clearance. This review highlights
the potential of LPHPs in pulmonary delivery of systemic drugs, with a focus on their critical attributes and
key formulation aspects. In addition, three examples of LPHPs under development are presented to emphasize the
potential of this technology to treat systemic diseases.
Keywords: PulmoSpheres, nanoparticle aggregates, porosity, dispersibility, aerodynamic diameter, systemic circulation.
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