Marangoni Driven Spreading on Entangled Polymer Subphases with Application to Pulmonary Drug Delivery

Carnegie Mellon University, Pittsburgh PA

Investigators

Abstract

0931057 Garoff This project will establish the fundamental wetting mechanisms required to harness surface tension gradient driven (Marangoni) flows to enhance spreading of drug delivered by aerosols in the lung. While inhaled aerosol drugs can deliver substantial doses of medication directly to the lungs, altered patterns of ventilation associated with diseased lungs cause inhaled drugs to deposit non-uniformly so that some lung regions receive very high local doses of medication while other regions go untreated. Preliminary studies suggest that the addition of surfactant to the aerosol will disperse these drugs more effectively after deposition. In the research, the PIs will identify the characteristics of surfactant formulations that optimize the efficacy of self-dispersing liquids for aerosol drug delivery. The research will build on prior research on the mechanism of spreading of exogenous fluids in the lungs of premature infants during Surfactant Replacement Therapies (SRT) but will differ in its focus in three ways. First, we focus on the final spread area of the formulation and, while not neglecting it, less on the dynamic mechanisms that lead to that final state. Second, they determine how the surfactant, the aqueous solvent, and the dissolved or solubilized surrogate drug in the droplets are distributed on the surface. Finally, the preliminary work strongly suggests a large separation in the time scales of the underlying processes in the spreading, such that the final spread droplet state is captured by a quasi-static interfacial tension balance on a flattened lens of the dosing fluid. The key to the most effective drug dispersal is to maximize the static lens area. Intellectual Merit: The discovery of effectiveness of SRT spawned considerable research into role of Marangoni flows in the airways. Theoretical analyses explored the ramifications of the complex subphases over which the transport occurs in the lungs, but experimental research focused on simpler systems. They will experimentally investigate key predictions of these analyses on rheologically complex subphases that could fundamentally alter the surfactant-driven spreading of fluids in the lung. In addition, prior work placed the emphasis on the dynamics of the initial spreading stages, but they turn the focus to the mechanisms that dictate the final disposition of the fluids, especially the dissolved or solubilized dyes that serve as model drugs. The refocusing of attention on the final state of the spread formulation represents a novel and potentially transformative approach to the problem. Broader Impacts: The results of the proposed research will guide the choice of surfactant formulations to be tested for self-dispersing carriers for aerosol drug delivery. This technology will benefit treatment of any number of obstructive lung diseases, including cystic fibrosis, asthma, pneumonia and other acute or chronic pulmonary infections. While this research focuses on fundamental physical mechanisms of enhanced drug spreading, the team collaborates with pulmonary medicine specialists in the University of Pittsburgh Medical School where our fundamental findings will guide in vivo studies. By regularly attending seminars and meetings with clinical investigators, the engineering and physics graduate students on this project will be trained in a highly interdisciplinary environment. They will mentor an undergraduate research student during each academic year and summer and at least two middle school students each year in the Carnegie Mellon/Colfax Physics Concepts Outreach Program.