The lung has the largest surface area of the human body in direct contact with the outside environment. With a surface area of ~ 70 m2 and an extremely thin alveolocapillary barrier, the lung forms an ideal absorptive site for inhaled macromolecules, and hence a promising portal of drug delivery. Meanwhile, the anatomical features of the lung also make the respiratory system the most susceptible to particle invasion. Accumulating evidence suggests direct correlations between particulate air pollutants and a number of pulmonary and cardiovascular diseases. Among the conventional particulate air pollutants, the potential toxicology of engineered nanomaterials, such as nanoparticles, which feature a particle size less than 100 nm in at least one dimension, has attracted increasing attentions, due to the nanotechnology boom in recent years.

Adverse health effects of inhaled particles. (The American Lung Association)

Once reaching the peripheral lung region, inhaled particles first interact with the surfactant lining layer of the lung, which acts as the first line of host defense against inhaled pathogens and other environmental pollutants. The fate of the inhaled particles and their potential cytotoxicity (i.e., interactions with lung epithelium cells) depend on their interactions with the lung surfactant film.

Effect of 1 wt% hydroxyapatite nanoparticles (HA-NPs) on the compression isotherms (a) and interfacial structure (b-e) of a natural pulmonary surfactant film (Infasurf) as a function of exposure time to the particles. (a) Significant time-dependent shift of compression isotherms to the left after exposure to the HA-NPs, indicating surfactant inhibition, i.e., more area reduction is required to increasing surface pressure. (b,c) AFM images of pure Infasurf at surface pressures (π) of 40 and 50 mN/m; (d,e) AFM images of Infasurf exposed to HA-NPs for 3 h at comparable surface pressures. The scan area of all AFM images was 50 x 50 μm. The Z-range was 5 nm for (b) and (d) and 20 nm for (c) and (e). The comparison of lateral structure shows variations to domain formation in surfactant monolayers (b vs d) and to organization of surfactant multilayers (c vs e), due to exposure to HA-NPs. See Fan et al. 2011. ACS Nano 5:6410.

In our lab, we use self-assembled surfactant monolayers as an in vitro model of studying both pulmonary drug delivery and potential toxicity of nanomaterials. We collaborate with experts in clinical, pharmaceutical, and materials areas on these studies.