Distribution of aerosols in mouse lobes by fluorescent imaging.
Better methods are needed to quantify the distribution of drug among the airways of the lungs of small animals to facilitate the development of agents that can target specific airways. Mice were exposed to aerosols of aluminum phthalocyanine tetrasulfonic acid (AlPCS) that ranged in concentration and size (0.2-2.8 μm). The trachea and lobes were removed and placed between glass slides, and fluorescent images were obtained at two different compression thicknesses. The intensity, normalized by the area, exposure time, and thickness, was then plotted as a function of compression thickness, from which the concentration and attenuation coefficient were estimated for each lobe and then for each pixel of the image. The latter was then used to generate an image reflective of the concentration. The lobe volume, concentration, and tissue attenuation of AlPCS was consistent among the lobes. The deposition fraction increased with decreasing particle size. The network of lines in the concentration image indicated that connective tissue has a lower concentration. The central airways were clearly evident in the images of mice exposed to the very small and large aerosols. This approach provides a rapid, economical means to obtain high resolution images of mouse lungs from which detailed analysis of the distribution of deposited aerosol particles can be obtained.
Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: yixxx106@umn.edu.
Dandan
D
Yi
Powerscope Incorporated, 1313 Fifth Street SE, Minneapolis, MN 55414, United States. Electronic address: anaqwi@powerscopetech.com.
Amir
A
Naqwi
Pediatric BMT and Pulmonary Medicine, University of Minnesota, Minneapolis, MN 55455, United States.
Angela
A
Panoskaltsis-Mortari
Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: wiedm001@umn.edu.
Timothy Scott
TS
Wiedmann
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007091:Image Processing, Computer-Assisted; D007211:Indoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D014132:Trachea / Q000378:metabolism*
D000336:Aerosols; D005456:Fluorescent Dyes; D007211:Indoles; D009942:Organometallic Compounds; C048577:aluminum tetrasulfophthalocyanine