title: Distribution of aerosols in murine obliterative bronchiolitis lungs by fluorescent imaging.
abstract: ABSTRACT  Background: Obliterative bronchiolitis (OB) is a major obstacle to the success of lung transplantation and is also a serious complication of hematopoietic stem cell transplant. It has few therapeutic options and respiratory delivery of potential therapeutic drugs is hindered by the narrowed and occluded airways.
  
  
  METHODS
  OB was induced in mice using an established protocol and lung function was assessed by plethysmograph. Mice were exposed to four different aerosols of aluminum phthalocyanine tetrasulfonic acid (AlPCS) that ranged in concentration and median particle size distribution (0.2-4.0 μm). The fluorescent intensity and number of pixels were measured for the trachea and lobes at two different compressional thicknesses. With analysis of the fluorescent intensity, the concentration and attenuation coefficient were estimated for each lobe and the trachea as well as individual pixels. The latter allowed generation of images reflective of the concentration.
  
  
  RESULTS
  Lungs/trachea from OB mice had lower deposition, which correlated with lung function measurements, and apparent greater variability in the intensity compared to controls. The estimated lung volumes measured by plethysmograph were not different between the OB group and controls; however, total inflational lung capacity was reduced in OB mice.
  
  
  CONCLUSIONS
  Despite the variability in disease induction, there is a clear link between aerosol deposition and lung function, which was revealed by fluorescent imaging. The modulation of aerosol deposition in lungs with restrictive airway disease underscores the importance of tailoring aerosolization to optimize drug delivery.
authors: Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors: Dandan
authors: D
authors: Yi
authors: Timothy Scott
authors: TS
authors: Wiedmann
authors: Amir
authors: A
authors: Naqwi
authors: Andrew Patrick
authors: AP
authors: Price
authors: Angela
authors: A
authors: Panoskaltsis-Mortari
mesh_terms: D000336:Aerosols / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D001989:Bronchiolitis Obliterans / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D010316:Particle Size; D012129:Respiratory Function Tests; D014132:Trachea / Q000473:pathology / Q000503:physiopathology
chemical_list: D000336:Aerosols; D005456:Fluorescent Dyes; D007211:Indoles; D009942:Organometallic Compounds; C048577:aluminum tetrasulfophthalocyanine