Development of drug delivery across the blood-brain barrier at a glance: A review

Central nervous system (CNS) diseases have widely affected death rate around the world. The lack of drug that reach the CNS due to the presence of blood brain barrier (BBB) is one of the biggest challenges causing the inadequate treatment outcomes. The BBB is a tight multi layered cell with efflux transporters that limits the transport of molecules including toxin, pathogens, and drug molecules into the CNS. Therefore, several drug delivery developments have been studied to enhance drug permeation across the BBB. A modulation of tight junctions (TJs) between BBB cells has shown an increase in BBB permeability. This modulation acts by applying TJs modulators that will reversibly open the TJs. There are other methods that can be applied to increase drug permeation, namely through the prodrug approach. The prodrugs can be made by adding specific functional groups into the main structure to repair the physicochemical characteristics of the drugs. The last methods is nanoparticles-based drug delivery system (NPs). The NPs, either was made by bottom-up or top-down technique, can facilitate drug transport by receptor-mediated endocytosis and minimize the retention effects due to their small size. The application of NPs for CNS drug delivery system leads to accumulation of the drug at the brain without getting metabolized.