Microfabricated Devices for Enhanced Bioadhesive Drug Delivery: Attachment to and Small-Molecule Release Through a Cell Monolayer Under Flow

The development of a novel microfabricated device for oral drug delivery that overcomes many of the common barriers present in the gastrointestinal tract is reported. Specifically, the attachment of targeting ligands, subsequent device binding, and small molecule release from the microdevices inflow are investigated. A diffusion chamber that permits the simultaneous study of particle binding and small-molecule release tinder physiologically relevant shear conditions is developed. It is observed that once the particles bind to the cell surface, they remain attached. A small fraction of the devices detach in flow; however, most of these devices readily reattach to the cell layer in a new location. This steady-state density of microdevices is most likely the result of larger order microdevice clusters releasing their loose interactions with nearby microdevices, shifting slightly downstream, and subsequently reattaching to the cell monolayer. The release of a model small molecule from microdevices over time is roughly linear and approximately ten times greater than that observed with the small molecule alone. Overall, the preparation and characterization of an oral drug-delivery microdevice system capable of both targeting and asymmetric release inflow is reported.