The Interfacial Physics Group

Carnegie Mellon University, Department of Physics

Spreading of Surfactant-Laden Aerosols on Entangled Polymer Solution Subphases

by Amsul Khanal

Abstract

For obstructive pulmonary diseases, such as cystic fibrosis (CF), aerosol drug delivery is a viable option to deliver drugs to infected airways. Current aerosol drug delivery techniques rely only on aerodynamics for drug dispersal inside of the lungs; however with limited ventilation and unusual aerodynamics in obstructed airways, various regions in the lungs are often left untreated. The mucus in such lungs can be highly viscous and unclearable, and can harbor bacterial infections in the absence of proper drug dispersal. Such infections can spread throughout the lung creating distress for patients and eventually may lead to mortality. We propose the use of surfactants to enhance pulmonary drug delivery. By enhancing surface transport via surface tension driven “Marangoni flows" along the airways surfaces after delivery, we expect surfactant-laden aerosols to produce a more uniform distribution of delivered drug in the lungs.

The research reported in this thesis determined the effects of different aerosol parameters on the maximum spreading of a deposited dye (a drug mimic) on entangled polymer solution subphases. The entangled polymer solution subphases served as mimics for the airway surface liquid (ASL) layer inside of the lungs. We roughly modeled deposition at a lung bifurcation by depositing the aerosol onto the subphase confined in a tube. The aerosol was direction perpendicular to the axis of the tube. We utilized a humidified bias gas ow to direct the aerosol to one end of the tube. This allowed us to distinguish direct and post deposition transport. We used fluorescence microscopy to determine the extent of spreading, and absorbance of the dye to determine the amount of aerosol formulation delivered. Aerosol droplet diameters were (1- 4 µm) within the range of sizes used clinically (1 - 5 µm).

We used previously established lung models and deposition probabilities to determine the aerosol deposition fluxes in the first sixteen airway generations. Comparing the results of these calculations to our experimental results, we determined that the aerosol delivery fluxes attained in our experiments spanned the deposition expected in 0 - 8 airway generations (large airways). When surfactant-laden aerosols are delivered onto the entangled polymer solution subphases at these fluxes, they provided enhanced spreading compared to their surfactant-free counterparts. The majority of the spreading occurred at short times post-deposition and plateaued at long times. We analyzed the dependence of spreading on various independent (surfactant concentration, ow rate and time of delivery) and dependent (surfactant mass and total delivered volume) variable. At the deposition rates in our experiments, aerosol droplets deposited on top of each other, forming a larger fluid body, In fact, the spreading of the fluid body formed from the multiple aerosol droplets was similar to the spreading of microliter scale drops deposition on the same subphases in the same geometry.