| Abstract
| - Uncontrolled agglomeration presents a formidable encumbrance to nanoparticle formulation as a dry powder forinhalation therapy. Spray-drying and freeze-drying of nanosuspensions has demonstrated some success in creatingdry powders composed of agglomerated nanoparticles with appropriate aerodynamic properties. These controlleddrying processes, however, may require an undesirable amount of excipient to maintain an active therapeutic whilegenerating dry powders and may not offer the desired control over agglomerate size and aerosolizability. As a potentialalternative approach, a method for flocculating nanoparticles in solution followed by freeze-drying is reported.Biodegradable poly(dl-lactic-co-glycolic acid) nanoparticles were self-assembled into flocs via electrostatic interactionsbetween nanoparticles coated with oppositely charged polyelectrolytes. The size of the nanoparticle flocs was readilycontrolled by manipulating the mixing ratio of charged nanoparticles. Freeze-drying the flocculated nanoparticlesproduced dry powders exhibiting low density (∼0.1 g/cm3), a weblike morphology, and desirable aerodynamic propertiessuited for dry powder aerosols.
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