Antibiotic-loaded nanoparticles have emerged as one of the most promising inhaled antibiotic formulations for treating bacterial biofilm infections in the lung. To effectively deliver the nanoparticles by inhalation, the nanoparticles are transformed into micro-scale dry-powder structures in the form of nanoparticle aggregates that can be easily aerosolized off the inhaler. Moreover, the nano-aggregates must readily reconstitute into the primary nanoparticles to be therapeutically effective upon their deposition in the lung. In the present work, respirable dry-powder aggregates of antibiotic-loaded polycaprolactone nanoparticles are produced by the spray-drying technique. The effects of the excipient formulation and drying temperature on the aqueous re-dispersibility, morphology, production yield, and flowability of the nano-aggregates are investigated. Three excipients commonly used in inhaled dosage formulation (i.e. mannitol, lactose, and leucine) and their combinations are examined. The results indicate that the nano-aggregate morphology is not greatly influenced by the excipient formulation, where low-density spherical nano-aggregates are consistently produced. The inclusion of hydrophobic leucine is mandatory to produce free-flowing particles, which however leads to decreased production yields. The aqueous re-dispersibility is strongly dependent on the excipient formulation, where only lactose-leucine formulations at particular nanoparticle to excipient concentration ratios are capable of producing re-dispersible nano-aggregates. (C) 2010 Elsevier B.V. All rights reserved.