Nanometer Layer Coating to Lactose Particles for Optimization of Dexamethasone Pulmonary Delivery.

Lactose (LA), the primary carrier in dry powder inhalers (DPIs), often exhibits excessive drug adhesion, which impairs aerosolization. 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-milled dexamethasone (DEX), NLC-LA 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-LA were confirmed by scanning electron microscopy, synchrotron radiation micro computed tomography and atomic force microscope. Continuous Leu coverage at nanometer-scale thickness was verified using Raman imaging, focused ion beam-scanning electron microscopy, time-of-flight secondary ion mass spectrometry, and synchrotron radiation x-ray microdiffraction. In vivo studies demonstrated that DEX DPI formulated with NLC-LA enhanced bioavailability and allowed a 30-fold dose reduction while maintaining therapeutic efficacy against high-altitude acute lung injury. Collectively, the NLC strategy bridges fundamental surface engineering with translational DPI performance, advancing inhalation science and formulation development.