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Pulmonary drug delivery system (PDDs) has been a research hotspot because the lung is an ideal absorptive position for both local and systemic therapy.Among the three general types of PDDs, dry powder inhalations (DPIs) possess superiority since it provides a more stable environment for active ingredients in solid state.However, one key issue for DPI is how to increase the drug delivery efficiency, especially for low-dose or expensive drugs.It is known that adhesion force between drug and carrier has great influence on DPIs performance,and lower adhesion results in higher deposition efficiency.The adhesion force is greatly influenced by the cartier surface roughness, and the adhesion force of carriers with different surface roughness ordered from low to high were nanometered topography, smooth surface and micrometered topography.The DPI carrier excipients, lactose and mannitol, often showed the micrometered roughness and smooth surface respectively for their spray-dried particles.Adding lubricant could help to reduce roughness of lactose particle, while how to increase the mannitol particles surface roughness is a critical problem.The purpose of this research is to create a nanometer topography surface carrier based on mannitol, intending to achieve higher drug deposition efficiency.Spray drying was employed to prepare carriers for DPIs, and water-soluble chitosan was selected to modify the physical properties of mannitol carriers.The obtained carriers were characterized by laser particle analyzer, scanning electron microscopy (SEM) and atomic force microscope (AFM) for the particle size and surface morphology.Density and repose angle (α) were assessed as well.DPIs were prepared by mixing micronized budesonide with spray-dried carriers at the ratio of 1∶10 (w/w), then the mixture was filled into hard hydroxyl propyl methyl cellulose (HPMC) capsules (3 #) at a dose of 10±0.5 mg/cap and the blend uniformity was tested.Single dose inhaler TurbospinTM and apparatus E (next generation impactor, NGI) was used to evaluate the delivery efficiency under standard conditions (European Pharmacopoeia 7.0).A nanometered topography surface of mannitol carrier was successfully achieved by blending with chitosan.While the roughness degree (Ra) of mannitol, chitosan, and mannitol-chitosan carrier were 19.8 nm, 5.23 nm and 72.8 nm, their fine particle fractions (FPF) were 32.94 ± 3.75, 20.79 ± 7.13 and 41.42 ±2.31%, respectively.This indicated there was a trend of logarithmic correlation between FPF and Ravalue (R2=0.9908).The particle size of the obtained carriers ranged from 2.59-12.73 μm, and the binary carrier possessed larger particle size than others.The tap density of mannitol, chitosan, and mannitol-chitosan carrier were 0.32, 0.39 and 0.14 g/cm3, respectively,which indicating the porous or hollow structure of the latter.It also showed obviously better flowability than single-component carriers, (their repose angle were 35.2±0.9, 54.2±3.5 and 47±4.4°, respectively, which was beneficial to further mixing and capsuling.An efficient and simple method was used to modify mannitol particles surface structure, and the formed nanometered topography surface could improve the pulmonary drug delivery efficiency for DPIs.