The access to the brain parenchyma is hindered by different physiological barriers that tightly regulate molecular trafficking. The blood-brain barrier (BBB), by regulating brain influx and efflux from the bloodstream, has a fundamental role in brain drug discovery and development. Indeed, numerous potential therapeutics fail to reach their molecular targets in the brain due to their inability to cross the BBB and/or to reach brain parenchyma in therapeutic concentrations. Nanotechnology-based approaches might improve the unfavorable pharmacokinetics of therapeutic molecules by enhancing binding to the cerebrovascular endothelium and translocation into the brain, thereby increasing delivery to target cells.
After a brief overview of the most relevant nanotechnology-based approaches engaged to deliver drugs to the brain, I will discuss a simple end effective strategy for enhancing uptake of lipid nanoparticles in the brain. Adsorption of apolipoprotein E4 onto polysorbate 80-stabilized nanoparticles to produce a protein corona allows the specific targeting of cerebrovascular endothelium. This strategy increased nanoparticle translocation into brain parenchyma, and improved brain nanoparticle accumulation 3-fold compared to undecorated particles. Apolipoprotein decorated nanoparticles have high clinical translational potential and may improve the development of nanotechnology-based medicine for a variety of neurological diseases.