(126a) Nanostructured Interfaces for Enhanced Biologic Transport and Immunomodulation

Drug delivery across epithelial barriers (oral, transdermal, mucosal) remains the preferred route for drug administration. However, therapeutic macromolecular drugs currently under development suffer from poor oral bioavailability, and consequently many of these macromolecules are delivered by injection. A variety of delivery paradigms have been developed, including chemical permeation enhancers, physical disruptors, and mucoadhesive materials, to enable more effective delivery of therapeutic macromolecules across epithelium but clinical utility has been limited thus far. Nanofabrication technology may offer potential advantages over conventional drug delivery strategies by enhancing molecular transport and local cellular response. The use of surface nanostructures, coupled to bulk materials, may permit enhanced transport of drugs, particularly protein therapeutics. In this talk, I will discuss the effect of nanostructured surfaces on the modulation of tight junction permeability and transport of key therapeutic molecules in vitro and in vivo. I will also discuss how nanostructures can be used modulate the immune microenvironment, presenting distinct biophysical cues to cells. The effect of geometry and the development of materials that can ultimately enhance therapeutic delivery is important for a broad range of diseases.