(668f) A Microfluidics-Based Approach to Model Drug Transport across 2D and 3D Biological Barriers

Most advanced therapeutics including proteins, peptides, nucleic acids and nanoparticles are administered via subcutaneous or intravenous injections. While these routes offer a logical entry point in the body, injected drugs must overcome numerous biological transport barriers to reach their intended target site. Animal testing is the gold standard of evaluating drug performance in pre-clinical research, but distinguishing delivery efficiency from drug efficacy is not trivial in such complex biological environment in vivo. On the other hand, traditional in vitro models such as the transwell plate often oversimplify the problem to a basic geometry and static flow conditions. Microfluidic devices can address these issues by capturing essential cellular activities in a controlled manner. In this talk, we discuss how to construct cell monolayers (2D) and cell networks (3D) on a chip with proper flow conditions to study the fate of drugs administered via injections.

Using a microfluidic chip, we created multiple cellular transport barriers that capture diffusion as well as flow-related transport barriers encountered by drugs after injections including diffusion across multi-component cell layers, vascular flow and adhesion to endothelium, among others. To quantify transport, we utilized fluorescent imaging techniques to determine concentration fields for solution-based drugs and number densities for particle-based drugs. Depending on the drug carrier used, we observed various responses of drugs interacting with cellular barriers. Thus, we can not only evaluate drug transport efficiencies, but also investigate their mechanism of action and gain fundamental understandings of the delivery process.