Abstract
Central nervous system (CNS) diseases are the leading causes of death and disabilities in the world. It is quite challenging to treat CNS diseases efficiently because of the blood–brain barrier (BBB). It is a physical barrier with tight junction proteins and high selectivity to limit the substance transportation between the blood and neural tissues. Thus, it is important to understand BBB transport mechanisms for developing novel drug carriers to overcome the BBB. This paper introduces the structure of the BBB and its physiological transport mechanisms. Meanwhile, different strategies for crossing the BBB by using nanomaterial-based drug carriers are reviewed, including carrier-mediated, adsorptive-mediated, and receptor-mediated transcytosis. Since the viral-induced CNS diseases are associated with BBB breakdown, various neurotropic viruses and their mechanisms on BBB disruption are reviewed and discussed, which are considered as an alternative solution to overcome the BBB. Therefore, most recent studies on virus-mimicking nanocarriers for drug delivery to cross the BBB are also reviewed and discussed. On the other hand, the routes of administration of drug-loaded nanocarriers to the CNS have been reviewed. In sum, this paper reviews and discusses various strategies and routes of nano-formulated drug delivery systems across the BBB to the brain, which will contribute to the advanced diagnosis and treatment of CNS diseases.
Highlights
Central nervous system (CNS) diseases, such as dementia, Alzheimer’s disease and gliomas, are the leading causes of disability and death [1,2,3,4]
The nanomaterial-based drug delivery systems functionalized with endogenous substances and essential nutrients for the brain, as well as their derivatives, are able to penetrate the blood–brain barrier (BBB) and deliver drugs to the brain via carrier-mediated transcytosis (CMT)
Drug nano-carriers with cationic molecules and ligand modified on their surface both illustrate higher BBB permeation and brain accumulation via adsorptive-mediated transcytosis (AMT) and receptor-mediated transcytosis (RMT), respectively
Summary
Central nervous system (CNS) diseases, such as dementia, Alzheimer’s disease and gliomas, are the leading causes of disability and death [1,2,3,4]. Nanomaterial-based drug delivery systems have been studied by exploiting physiological BBB transport (transcytosis mechanism). The electrical resistance of brain endothelium is much higher than other endothelial cells, which introduces even further limitations in paracellular transport [9] Due to these structural limitations, almost all substances could not cross the BBB via transcellular transport. Substances cross the BBB by following one of the four transport mechanisms: passive diffusion, carrier-mediated transport, adsorptive-mediated transcytosis, and receptormediated transport (Figure 2). Instead of having transmembrane transporter, peptide receptors on the cell membrane mediate transcytosis of the ligands This mechanism works for blood-to-brain transport, brain to blood transport, and blood-to-brain capillary endothelium transport without the export into the brain parenchyma [9]
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