Completed notes of the course Part 2

Pagina 1

LEZIONE 01-04-19 BBB TRANSPORT It’s very important to find a way to cross this barrier, because it’s the only way to deliver drugs to the brain. Tight junctions? Big particles can’t pass, small ones could pass but the barrier has developed a way to pump back these drugs once adsorbed. We could use active transport: endocytosis and transcytosis are the mechanisms to study: we have a nanoparticle that targets a receptor and so the passage is allowed. There are several examples of nanoparticles crossing this barrier. We may have the stealth nanoparticle. Gene NP means that it transports DNA or RNA. The particle, which could be also peggilated, could be functionalised with a monoclonal antibody generating an active phase, so that it can bind the transferring receptors on the BBB. There is an energy dependent endocytosis, the particle will be entrapped in the vesicle and then we’ll have transcytosis (released on the other side inside the brain). MOST FAMOUS EXAMPLE In the 90s they used PBCA, which wasn’t so biocompatible, but it was one of the few available. It’s coated with a hydrophilic surfactant: you remove the solvent and obtain the particles. The particle is made of And they use a non-ionic surfactant, which has a hydrophobic tail and branches of PEG. The hydrophobic component sticks onto the surface of the nanoparticles, whereas the hydrophilic block stays on the water surface stabilising the particles. They proved that these particles were able to cross the BBB. The hydrophobic surface adsorbed the lipoprotein E, largely present in our blood, it transports cholesterol in the BBB. So the BBB has ApoE receptors, it’s internalized by entocytosis. As a consequence, the synthetic particles with ApoE were able to be adsorbed. This material is not so compatible, it’s been…