STTR Phase I: Active Transport of Caffeine through a Blood-Brain Barrier Model

The broader impact of this Small Business Technology Transfer (STTR) Phase I project is to create a drug-discovery platform that will screen quickly and early in the process for candidate therapeutics that can enter the central nervous system (CNS). The goal is to minimize the lengthy and expensive clinical trials that ultimately fail because of their failure to enter the BBB by providing a high assurance that the drug can pass the blood/brain barrier (BBB). The project will facilitate discovering next-generation interventional treatments for serious brain-related diseases and will greatly benefit patients and families fighting debilitating diseases that are difficult or impossible to treat with current methods. The ability to screen for BBB penetration early is needed. An estimated 2% of small drug molecules and no large molecules are able to pass into CNS to treat neurodegenerative diseases, multiple sclerosis and strokes, accounting for 12% of total global deaths. Each of these diseases represents a major healthcare cost and caregiver burden. The proposed project focuses on mimicking the BBB. This work will utilize cylindrical hydrogels to provide three distinct regions for the growth of multiple types of cells related to the BBB, thereby providing an environment that is similar to the native system. This will provide a highly relevant model to visualize the active transport of bioactive molecules across the BBB to create effective, next-generation therapeutics for use in the CNS. One goal is to show cell survival throughout ten-day-long trials. Additionally, the genetic response of the cells within the system will be analyzed to better understand their behavior, and the system’s inherent conductivity will show real-time cell-to-cell communication. Once a model is created, the transport of caffeine across the model barrier will be studied and compared with known values of how the molecule acts within the body to begin validating the system. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.