A Novel Physicologically Realistic Microfluidic In-vitro Blood-brain Barrier Mode

DESCRIPTION (provided by applicant): The overall objective of this study is to develop a novel in vitro microfluidic platform to test a drug or delivery vehicle's ability to permeate the Blood-Brain Barrier (BBB). In contrast with current large-sized, static incubation techniques, our proposed device comprises of a microfluidic two-compartment chamber. The chamber is designed in such a way as to permit visualization-friendly evaluation of transport/permeation under appropriate microcirculatory size and flow conditions, while simultaneously simplifying device fabrication. The apical side is seeded with endothelial cells (demonstrated for permeability and flux assays) and the basolateral side supports glial cell co-cultures. The increased physiological realism will substantially improve BBB characteristics including formation of tight junctions and expression of relevant transporters. The new platform offers greater throughput, increased library coverage, lower cost, rapid turnaround times and increased mechanistic knowledge benefiting drug discovery efforts. Phase I study seeks to develop a prototype of the microfluidic BBB, adapt protocols for culturing endothelial cells and will culminate with a clear demonstration of improved barrier function. Chip and culture optimization as well as in vivo validation are planned for Phase II. A multi-disciplinary partnership with expertise in cellular BioMEMS (CFDRC) and BBB Models (Vanderbilt University) has been formed. PUBLIC HEALTH RELEVANCE The project seeks to develop an in vitro screening model for screening the potential of drug candidates to cross the BBB and subsequently cause therapeutic or toxic effects. By providing accurate and predictive data, the model will reduce the need for animal models and promises to both reduce late stage drug candidate failures and accelerate central nervous system (CNS) therapeutic development. The product will be commercialized to pharmaceutical firms, drug research labs and universities/non-profit centers engaged in novel neurological therapeutics research and CNS toxicity. Equally important, it is also expected to spur basic research, where it can be used to study the biological mechanisms of BBB (dys) function.