Nanotherapeutic Strategies for Overcoming the Blood-Brain Barrier: Applications in Disease Modeling and Drug Delivery

The blood-brain barrier (BBB) is the main obstacle preventing access to the central nervous system (CNS). It is therefore a major challenge in CNS studies, e.g., investigations of novel therapeutic agents for brain tumors, such as glioblastoma multiforme (GBM). Ensuring the structural and functional integrity of the BBB is essential for such studies. Therefore, the BBB and blood-brain-tumor barrier (BBTB) behaviors must be further investigated to enhance the treatment effectiveness in neurodegenerative diseases (NDDs). Researchers are striving to use nanoparticles (NPs) and/or develop nano delivery systems (NDSs) to efficiently overcome the barriers to transporting neurotherapeutics to the brain, focusing on targeting disease or tumor sites. In this regard, BBB disease modeling enables examination of the transport of these molecules and/or systems from the bloodstream to the brain. Facilitating their transport is likely to enhance their investigation in CNS studies and potentially lead to their use in treating various NDDs. This review describes the BBB, NPs, and/or NDSs used in BBB studies and evaluates the ability of existing BBB disease models to precisely forecast the in vivo efficacy of NPs or NDSs.