Introduction - Lung Disease and Drug Delivery

Each time we breathe, we inhale air into our lungs that contains small particles of dust and pollen, as well as harmful viruses and bacteria. Our bodies have devised clever ways to deal with this constant bombardment by trapping and removing this foreign material, including:

¤ tortuous airways that filter out large particles

¤ mucociliary clearance that removes large particles from the upper airways
towards the throat, where they are swallowed

¤ immune cells that can recognize many foreign materials and destroy them

But, what happens when these defense mechanisms fail or when our bodies are overwhelmed by the inhaled material? Inevitably, we get sick. In an ideal world, we would treat only the lungs by delivering the appropriate drug to the site of the problem, such as has been done successfully with asthma. However, this is not always easy to do. The mechanisms that the body has in place to keep out harmful material also makes it difficult to get helpful drugs into the lungs. This is where aerosol scientists and engineers step in. By understanding the interactions between the drugs we want to deliver and the biology of the lungs, we can devise new strategies to outsmart and cure the body. This is the fascinating world that I and many other researchers study every day.

Research Interests

Aerosols that Mimic Bacterial Infection

Our group is designing multifunctional aerosol particles to target drugs to the lung epithelium. To achieve this, the particles are coated with bacterial ligands that enable the particles to attachment to lung tissues. This approach can provide better treatment for diseases that directly affect the pulmonary tissues such as lung cancer, cystic fibrosis, and cell-penetrating pathogens. This work is supported by the NIH.

Dry Powder Aerosols to Treat Respiratory Biofilms

Bacterial biofilms are communities of bacteria that form when the bacteria adhere to a surface in an aqueous environment and begin to excrete a protective polysaccharide matrix that holds the biofilm together. Bacterial biofilm formation in the lungs is a major concern for humans who have cystic fibrosis (CF), are immunocompromised, or are on mechanical ventilation. While aggressive therapies combining multiple antibiotics with mucus modulators alleviate some acute symptoms caused by biofilm infections in the lungs, the infection is not completely eradicated due to the protection afforded by biofilm formation. To combat pulmonary bacteria biofilms, we are developing dry powder aerosols that deliver compounds that can disperse the bacteria from within the biofilm, thereby enhancing the ability of antibiotics to eradicate the bacteria. Support for this work has been provided by the NIH and the PhRMA Foundation.

Mucus Mimetics to Study Biointeractions

We have ongoing work that is focused on the development of mucus simulants that match the chemical composition, bulk physical properties, and surface properties of native mucus. Using mucus simulants gives us the ability to conduct large-scale studies and to explore a wide range of mucus properties. Our focus on controlling the surface properties of the fluids is particularly unique in our approach, enabling us to study lung relevant surface phenomena. 

Aerosol Interactions with Pulmonary Fluids

Our work in this area focuses on the interactions of deposited particles with pulmonary fluids at the air-fluid interface. Using mucus mimetics, we are studying how particles transport along or across the interface. A better understanding of these transport processes will aid our ability to predict and control the transport behavior of aerosols in the lungs and to determine why certain medical aerosols may fail to provide adequate treatment. We are also investigating the effects of engineered particles on pulmonary surfactant interfaces. Through these studies, we aim to determine the mechanisms by which deposited particles alter the normal function of pulmonary surfactant. Funding for this work has been provided by the Environmental Health Sciences Research Center at UI.