(156f) Dendrimer Nanocarriers for Transport Modulation Across the Pulmonary Epithelium: Cellular Internalization, Transport and Formulation in Portable Inhalers

The ability to modulate the transport of therapeutics across the pulmonary epithelium may provide new opportunities in terms of improving the treatment of regional lung diseases, and also in the development of new strategies for the systemic delivery of therapeutics through the lungs using the oral inhalation (OI) route.  The lungs are an attractive pathway to the bloodstream as they have a large surface area, consist of a thin cellular barrier, and have lower proteolytic activity compared to those observed in traditional delivery routes.

In this work, the effect of PEGylation on the cellular internalization and transport of amine-terminated, polyamidoamine dendrimer nanocarriers across an in vitro model of the human airway epithelium (Calu-3 cells) was evaluated.  Our results indicate that an increase in the density of PEG grafts onto the surface of dendrimer nanocarriers enhances their transport across polarized Calu-3 monolayers, and can also be used to tune their cellular uptake.  We also demonstrate that these dendrimer nanocarriers can be formulated in portable inhalers (pressurized metered-dose inhalers), and that these suspensions possess enhanced aerosol characteristics, which are conducive to deep lung deposition.