title: Aerosol delivery of nanoparticles in uniform mannitol carriers formulated by ultrasonic spray freeze drying.
abstract: OBJECTIVE
  While most examples of nanoparticle therapeutics have involved parenteral or IV administration, pulmonary delivery is an attractive alternative, especially to target and treat local infections and diseases of the lungs. We describe a successful dry powder formulation which is capable of delivering nanoparticles to the lungs with good aerosolization properties, high loadings of nanoparticles, and limited irreversible aggregation.
  
  
  METHODS
  Aerosolizable mannitol carrier particles that encapsulate nanoparticles with dense PEG coatings were prepared by a combination of ultrasonic atomization and spray freeze drying. This process was contrasted to particle formation by conventional spray drying.
  
  
  RESULTS
  Spray freeze drying a solution of nanoparticles and mannitol (2 wt% solids) resulted in particles with an average diameter of 21 ± 1.7 μm, regardless of the fraction of nanoparticles loaded (0-50% of total solids). Spray freeze dried (SFD) powders with a 50% nanoparticle loading had a fine particle fraction (FPF) of 60%. After formulation in a mannitol matrix, nanoparticles redispersed in water to < 1 μm with hand agitation and to < 250 nm with the aid of sonication. Powder production by spray drying was less successful, with low powder yields and extensive, irreversible aggregation of nanoparticles evident upon rehydration.
  
  
  CONCLUSIONS
  This study reveals the unique advantages of processing by ultrasonic spray freeze drying to produce aerosol dry powders with controlled properties for the delivery of therapeutic nanoparticles to the lungs.
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Pharmacy Building A15, Camperdown, New South Wales, 2006, Australia.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: D'Addio
authors.forename: John Gar Yan
authors.initials: JG
authors.lastname: Chan
authors.forename: Philip Chi Lip
authors.initials: PC
authors.lastname: Kwok
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Benson
authors.forename: Robert K
authors.initials: RK
authors.lastname: Prud'homme
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
mesh_terms: D000336:Aerosols / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005612:Freeze Drying / Q000379:methods*; D008353:Mannitol / Q000737:chemistry*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011208:Powders; D014465:Ultrasonics / Q000379:methods*
chemical_list: D000336:Aerosols; D004337:Drug Carriers; D011208:Powders; D008353:Mannitol
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