Imaging extra-thoracic airways and deposited particles in laboratory animals Praveen K. Srirama, Chris D. Wallis, DongYoub Lee, Anthony S. Wexler n Air Quality Research Center, University of California, 3050 Bainer Hall, One Shields Ave., Davis, CA 95616, United States article info Article history: Received 7 April 2011 Received in revised form 4 September 2011 Accepted 22 October 2011 Available online 29 October 2011 Keywords: Nasal deposition Drug delivery Air pollution Imaging Fluorescent particles Cryomicrotome abstract Laboratory animals are widely used as models for exploring adverse and beneficial health effects caused by inhalation of suspended particles. Mapping particle deposition throughout the airways of laboratory animals is crucial since the location of particle deposition often determines subsequent clearance, transport and the health effects elicited. Such mapping has yet to be performed systematically due to lack of available methods. In this paper, a new method is presented for imaging both the nasal airways of laboratory animals and particles deposited in them. After inhalation of particles, the rat airways are frozen to lock the particles in place and cast at this temperature to color and support the lumen. Once the cast is cured, an imaging cryomicrotome sections and images the airways as well as the deposited fluorescent particles. Computer software reconstructs the airways and particle maps from these serial images. The method was validated by manually placing boluses of fluorescent particles in nasal airways of a rat and then imaging them to ensure that they were displayed in the correct locations. To demonstrate the method, rats inhaled 2.5 mm particles in a nose-only exposure chamber. Images and reconstructions are presented of the nasal passage and deposited particles for one of these rats demonstrating the method’s usefulness for locating inhaled and deposited therapeutic and toxic particles in the extra-thoracic airways of laboratory animals. & 2011 Elsevier Ltd. All rights reserved. 1. Introduction The anatomy and physiology of the nose is well suited for drug delivery due to its large surface area, high total blood flow, rich vascular epithelium, avoidance of first-pass metabolism and porous endothelial basement membrane (Illum, 2000; Mathison et al., 1998; Mygind & Dahl, 1998; T¨ urker et al., 2004; Ugwoke et al., 2005). Other benefits of nasal delivery include low cost, low dose, self-medication, non-invasiveness, patient convenience, comfort and compliance (Hussain, 1998). Drug companies are extending life cycle and patent expiration of existing medical products by reformulating them for nasal drug delivery and other alternate routes (Mathias & Hussain, 2010). Current research is being conducted in nasal delivery of drugs to treat a wide variety of diseases such as nasal congestion, nasal allergy, nasal infection, pain, panic attacks, Parkinson’s disease, diabetes, growth deficiency, osteoporosis and nausea (Illum, 2003; Jiang et al., 2010). Various beneficial and adverse health effects of inhaled particles can be better understood by locating their patterns of deposition in the nasal passages. With respect to pharmaceutical aerosols, the location determines whether the aerosolized Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/jaerosci Journal of Aerosol Science 0021-8502/$ - see front matter & 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jaerosci.2011.10.007 n Corresponding author. Tel.: þ530 754 6558; fax: þ530 754 8771. E-mail address: aswexler@ucdavis.edu (A.S. Wexler). Journal of Aerosol Science 45 (2012) 40–49