Nanoparticles at the neurovascular unit: in vitro and in vivo studies to assess the blood-brain barrier permeability and function

The brain is always confronted with the dilemma of the protection from noxious substances from the blood and the delivery of vital metabolites. Endothelial cells, forming together with other cells the blood-brain barrier (BBB), are known as the “gatekeepers” of this trafficking. It is known that many common drugs cannot cross the BBB in appreciable concentrations, thus decreasing the rate of possible available treatments for many central nervous system (CNS) diseases. In the last decades, nanomedicine has increase its role in developing strategies to deliver drugs to the CNS. In our previous studies we administrated liposomes functionalized with phosphatidic acid and an ApoE-derived peptide as a potential treatment for Alzheimer’s disease (AD): their administration reduced brain beta-amyloid burden and ameliorated impaired memory in AD mice. Furthermore, we evaluated the adaptability of warm microemulsion process for ligand surface modification of solid lipid nanoparticles with ApoE to target the BBB and we investigated how the different administration routes affect their brain bioavailability. The aim of this study is to evaluate the interaction of lipid based nanoparticles (NPs) at the neurovascular unit. In light of our previous results we here assess the NPs interaction with human cerebral microvascular cells (hCMEC/D3) as in vitro BBB model and mice brain neuronal slices by means of patch clamp recordings and simultaneously calcium imaging measurements to follow calcium dinamics transients. Our studies of the NPs impact to the main neurophysiological functions should encourage further applications of NPs based drug delivery strategies for future clinical treatments of CNS diseases