The influences of physicochemical properties of lactose microcarrier on the pulmonary inhalation performance of polymeric nanoparticles were unknown. The effects of size, size distribution, specific surface area, surface roughness, crystallinity, and fine content (<5 mu m fraction) of lactose microcarrier on inhalation profiles of rifampicin encapsulated in polyvinylpyrrolidone nanoparticles were investigated. The spherical lactose was modified through solvation and reprecipitation processes using aqueous ethanolic solution. Its blends with rifampicin-polyvinylpyrrolidone nanoparticles were subjected to cascade impactor analysis as a function of the lactose properties. The unprocessed lactose carried nanoparticles through surface adsorption and pore immersion methods. The small, less crystalline and elongated processed lactose carried nanoparticles through microaggregating the nanoparticles with its fine content, and encapsulation within lactose aggregates made of larger primary nuclei. The latter improved the fine particle dose, fine particle fraction, percent dispersed, percent inhaled of nanopartides due to their ability to remain attaching to lactose during aerosolization, and detach for deep lung deposition in late time domain. Overall, the dispersion and inhalation efficiency of nanoparticles improved with smaller, more amorphous and elongated lactose. Given the prism geometry, the processed lactose with rougher surfaces performed better. (C) 2017 Elsevier B.V. All rights reserved.