Abstract: Cystic fibrosis is a life-shortening genetic disease that affects the respiratory, digestive and reproductive systems. Though it manifests a variety of symptoms, it is most notably characterized by chronic pulmonary infections that ultimately lead to respiratory failure and premature death. Recent research has focused on developing inhaled aerosol antibiotics to treat such infections; however, current formulations use saline liquid carriers that are unable to to fully disperse the drugs throughout the lungs, as saline’s surface tension is higher than that of the airway liquid surface. Given that certain lipid surfactants are capable of lowering the surface tension of aqueous solutions, our hypothesis is that a surfactant-based liquid carrier could greatly improve pulmonary drug dispersion and efficacy to better treat lung infections. Previous work both in vitro and in a small group of cystic fibrosis patients has led to the creation of an optimized, self-dispersing inhaled carrier formation that significantly enhances aerosolized drug spreading under very specific, laboratory conditions. The aims of this project are to develop an in vivo imaging model to assess pulmonary drug dispersion, and then to use this model to determine if our surfactant-based formulation also improves drug dispersion in a murine model.
To model drug dispersal in the lungs, we instilled BL/6 mice with a combination of fluorescent dye and either water or surfactant, and then measured the amount of fluorescence in different regions of the lungs. We then calculated the ratio of fluorescence in the peripheral lung regions to the total fluorescence in the lungs, and used this to compare the mice instilled with water/dye solution to those instilled with surfactant/dye solution. Though our results lack statistical significance, they suggest that our candidate surfactant may improve drug dispersion in murine lungs. Further studies are needed to confirm these conclusions. To aid in future antibiotic treatment studies, we also modeled aerosolized Klebsiella pneumoniae infection in mice.
Last Updated On Thursday, April 6, 2017 by Malenka, Judith Ann
Created On Thursday, March 30, 2017
Click to enter calendar events or share school news and announcements.