Hollow spherical aggregates of biocompatible silica nanoparticles are produced by the spray drying technique to facilitate the delivery of the nanoparticles to the lung for potential drug delivery applications. The large geometric size (d(G)> 5 mu m) and the low density (rho(eff)approximate to 0.3 g/cm(3)) of the nano-aggregates are specifically formulated to achieve high aerosolization efficiency and an effective lung deposition. The nano-aggregates must readily re-disperse into the primary nanoparticles in an aqueous medium for the nanoparticles to perform their intended therapeutic functions. An aqueous re-dispersibility characterization technique based on the turbidity level measurement is developed for this purpose. A water-soluble excipient (i.e. mannitol), which forms "excipient bridges" interconnecting the nanoparticles. is included in the spraydrying formulation to produce readily re-dispersible nano-aggregates. The nano-aggregate aqueous re-dispersibility depends on (1) the silica: mannitol concentration ratio and (2) the degree of hollowness, where nano-aggregates with a higher shell thickness to particle radius ratio exhibit weaker re-dispersibility due to the poor particle wetting. The spray-drying condition and the silica: mannitol ratio, which lead to the production of highly re-dispersible nano-aggregates having the desired morphology, are determined. The promising results signify the potential application of hollow spherical silica nano-aggregates as an inhaled drug delivery vehicle. (C) 2009 Elsevier B.V. All rights reserved.