Microfluidic modeling of the effects of nanoparticles on the blood-brain barrier in flow

The difficulty of diffusing drugs across the blood-brain barrier (BBB) has caused an impasse for many brain treatments. Nanoparticles (NPs), to which drugs can adsorb, attach, or be entrapped, have the potential to deliver drugs past the BBB. Before nanoparticles can be used, their effects on the BBB and brain must be ascertained. Previous steady-state studies fall short for closely modeling \textit{in vivo} conditions$.$ Convection of nanoparticles is ignored, and endothelial cells' (ECs) morphology differs based on loading conditions; \textit{in vitro} loading with continuous flow exhibit ECs indicating a more similar \textit{in vivo} phenotype. NPs interact with monocytes prior to the BBB, and their toxicity effects were measured in flow conditions using both Trypan Blue cell counting and cell proliferation assays. The microfluidic device designed to model the BBB contained a concentric PES hollow fiber porous membrane in PFA tubing. Full use of the device will include ECs adhered on the inner surface and astrocytes adhered to the outer surface of the PES membrane to model cerebrovascular capillaries.