This goal of this project is to improve aerosol-based drug delivery systems for people with obstructive lung disease. The distribution of aerosol-based drugs is strongly affected by airflows in the lung. Controlling the size and density of drug-containing aerosol droplets can ensure drugs penetrate deep and distribute uniformly throughout the lungs. However, airflow patterns are altered when lungs are obstructed by excess mucus deposits or airway constrictions, and aerosol droplets deposit on or upstream of obstructions. This project will investigate an alternative strategy that maximizes dispersal of drugs after the aerosol droplets have landed on the lung airway surface. Surfactant molecules will be incorporated into the aerosol droplets so that the surface tension near droplets after they land will vary along the lung surface. The gradient in surface tension will induce a flow in the thin airway surface liquid (ASL) films that line the airways. Flow in the ASL will carry drugs past obstructions. However, if the surface tension gradient exceeds a critical value, the ASL film may rupture, leaving a dry patch on underlying tissue that would diminish drug dispersal. This project will assess phenomena that influence film rupture and address its effects on drug transport. The results of this research will provide the fundamental knowledge needed to design aerosols that will enhance distribution of drugs for many obstructive lung diseases, including cystic fibrosis, pneumonia, and acute or chronic pulmonary infections. Undergraduates and graduate students will join a multidisciplinary team to carry out the research and to mentor middle school students who will perform experiments exploring physical processes in medicine, under the Carnegie Mellon/Colfax Physics Concepts Outreach Program.
This project will address two unstudied phenomena in model systems that represent the crucial Marangoni flow hydrodynamics for aerosol-based drug delivery. The first is prompted by a recent discovery of the detailed structure of the two-layer ASL. Consisting of densely tethered mucin chains, the bottom layer of the ASL resembles a fluid-saturated porous medium. Slip at the interface between the upper fluid layer and the porous medium is hypothesized to retard dewetting, and fluid flow out of the porous medium may promote rewetting. Experiments and modeling will quantify how the lower layer porosity affects dewetting and rewetting transitions for films of varying thickness and varying surface tension gradients. The second phenomenon addresses the coupled roles of geometry and gravity. In a planar geometry, the dewetting transition is dictated by a balance of Marangoni, or surface tension gradient, stresses and gravitational stresses. The effect of gravitational orientation on Marangoni forced dewetting has not been considered previously even though multiple orientations are present for Marangoni flows on the inner wall of a cylindrical conduit. Experiments and modeling will quantify how dewetting transitions vary with deposition locus, cylinder radius and cylinder orientation in Marangoni flows inside a film-coated cylindrical tube that mimics a lung airway. An optical technique will be used to track quantitatively the evolution of film height profiles and reveal occurrences of dewetting or rewetting. This will be coupled with separate measures of soluble dye (a drug mimic) advection by the Marangoni flow. Models developed for the project will be tested in experimentally accessible conditions and then used to predict behaviors in the conditions more typical of the lung.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
