A dynamic in vitro model of blood-brain barrier: effect of different polymeric nanoparticles on the crossing ability

The blood–brain barrier (BBB) remains a critical bottleneck for Central Nervous System (CNS) drug delivery. While polymeric nanoparticles (NPs) are promising carriers, their development requires advanced screening platforms. This work focuses on the development and validation of a dynamic in vitro BBB model for testing future nanotherapeutics, rather than proposing a specific optimized nanosystem. Although simplified compared to in vivo conditions, this model enables controlled evaluation of endothelial permeability and transport dynamics. By incorporating flow conditions, we investigated how shear stress influences the translocation of PLGA and chitosan NPs, selected for their well-documented contrasting properties. Results show that the fluid-dynamic environment effectively discriminates NPs permeability without toxicity, highlighting the role of surface charge and polymer nature. This study establishes a versatile tool for the standardized evaluation of brain-targeted delivery.