There is an urgent need for novel inhalable drug carriers to fight respiratory infections. Lipid-coated mesoporous silica particles (LC-MSPs) combine the biocompatibility of lipids with the aerosolization properties of micronized low-density MSPs. In this study, the abundant lung surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC) was used to coat disordered MSPs by means of two methods: vesicle fusion (VF) and spray-drying (SD). FT-IR and TGA analyses indicated the presence of the lipid coating, while SEM images revealed spherical particles with a smooth, homogenous surface and no detectable lipid aggregates. Both the VF and SD methods resulted in full phospholipid coverage on the outer silica surface (>100 %). However, the VF method produced a more homogeneous coating across particles and achieved a higher lipid content compared to SD (7.0 vs 3.0 % w/w). The resulting LC-MSPs exhibited favorable aerosolization properties, enabling efficient pulmonary delivery of clofazimine, a lipophilic antitubercular drug. The DPPC coating promoted interaction with endogenous lung surfactant, which enhanced the dispersion of the particles in the alveolar environment and significantly increased drug dissolution (from 35 to 75 %). Lipid coating significantly enhances particle adhesion and penetration across the human bronchial mucus layer and into the underlying tissue. Overall, our study presents a refined formulation strategy using phospholipid-coated MSPs as a single-component dry powder carrier, offering targeted lung deposition, enhanced drug dissolution, mucoadhesion, and tissue penetration.