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In this study, four coating methods solid mixing, vapor deposition, suspension coating, and solution coating were evaluated to modify LA surfaces. Solution coating with leucine (Leu) proved optimal and was defined as Nanometer Layer Coating (NLC). When blended with jet\u2010milled dexamethasone (DEX), NLC\u2010LA increased the fine particle fraction from 20% to 50% and improved flowability, reducing Carr's Index to 24%. Reduced adhesion forces and increased surface smoothness of NLC\u2010LA were confirmed by scanning electron microscopy, synchrotron radiation micro computed tomography and atomic force microscope. Continuous Leu coverage at nanometer\u2010scale thickness was verified using Raman imaging, focused ion beam\u2013scanning electron microscopy, time\u2010of\u2010flight secondary ion mass spectrometry, and synchrotron radiation x\u2010ray microdiffraction. In vivo studies demonstrated that DEX DPI formulated with NLC\u2010LA enhanced bioavailability and allowed a 30\u2010fold dose reduction while maintaining therapeutic efficacy against high\u2010altitude acute lung injury. Collectively, the NLC strategy bridges fundamental surface engineering with translational DPI performance, advancing inhalation science and formulation development.<\/jats:p>","DOI":"10.1002\/advs.76929","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:23:12Z","timestamp":1785756192000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nanometer Layer Coating to Lactose Particles for Optimization of Dexamethasone Pulmonary Delivery"],"prefix":"10.1002","author":[{"given":"Qin","family":"Nie","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis School of Pharmacy Shenyang Pharmaceutical University  Shenyang China"},{"name":"Center for Drug Delivery Systems Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 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