Unlocking the human blood-brain barrier (BBB) characteristics for the development of nano-delivery strategies for central nervous system therapies

The Blood-brain barrier (BBB) is a crucial obstacle preventing substances from entering the central nervous system (CNS). The BBB is selectively permeable, and understanding its heterogeneous structure and functional integrity is crucial for BBB studies. The characterization and enhanced modeling of the BBB requires extensive research. Studies using in vitro BBB models, including those based on omics methods, have been aimed at determining the cellular and molecular mechanisms involved in BBB development, and assessing BBB characteristics. Moreover, BBB behaviors and essential factors must be understood to enable the development of in vitro BBB models for the analysis of BBB penetration strategies, such as nanoparticles (NPs) and nanodelivery systems (NDSs). This review discusses properties of the BBB, including factors and cells affecting its formation, integrity, and transport mechanisms (pathways), as well as characterization assays. Furthermore, molecular analysis of the BBB, the types of cells used to construct in vitro BBB models, and existing in vitro BBB and disease models are described. Important aspects regarding future BBB modeling for nano-based studies are also addressed.