In the search for a viable approach to deliver therapeutics across the BBB, a number of prerequisites must be fulfilled. In addition to transmembrane diffusion, some macromolecules, such as transferrin, are able to cross the BBB via a receptor-mediated process. Other molecular characteristics that can affect the partitioning of a drug molecule between the blood and the brain include molecular charge, tertiary structure and degree of protein binding. These phenomena, are mostly observed for low molecular weight and high lipid solubility are favored. Of the drugs that are able to cross the BBB, most do so via transmembrane diffusion, a mechanism that depends on the drug’s structural or chemical link to the cell membrane, and on integration or permeability through it.
Indeed, most CNS drug candidates, essentially 100 % of large-molecule drugs and about 98 % of small-molecule drugs, cannot autonomously penetrate the BBB, and therefore, they also cannot access the brain. As such, the BBB has been an obstacle to the development of new drugs for the CNS. Present in all organisms with a developed CNS the BBB not only prevents harmful agents from penetrating the CNS, it also blocks the delivery of drugs and therapeutics to the CNS. Rigorous control of the brain microenvironment, essential to support neural signaling within the central nervous system (CNS), is provided by the blood-brain barrier (BBB). Ion channel blockers can be used to control the transport of AuNPs. A major amount of gold resides in blood vessels therefore perfusion required. ConclusionsīBB penetration by AuNPs is spontaneous without the application of an external field. Possible mechanisms for the transport of AuNPs through the BBB are discussed. A biological half-life of 12.9 ± 4.9 h was found for the gold nanoparticles. Injection of Na, K or Ca ion channel blockers reduced BBB penetration by half. After perfusion the concentration of gold in brain regions diminished dramatically indicating that most of the gold was in venous blood and not in the brain tissues. Injection of AuNPs to the abdominal cavity of rats resulted in levels of gold found in blood, urine, brain regions and body organs. Here we proved that gold nanoparticles (AuNPs) penetrate the BBB in rats to reach brain regions.
Research efforts to identify viable routes of BBB penetration have focused on structures such as micelles, polymeric nanoparticles and liposomes as drug carriers, however, many of them failed to provide unequivocal proof of BBB penetration. The blood brain barrier (BBB) controls the brain microenvironment and limits penetration of the central nervous system (CNS) by chemicals, thus creating an obstacle to many medical imaging and treatment procedures.
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