Ligand-mediated transport of drug delivery devices across the blood-brain barrier

PhD ceremony: Ms. J.V. Georgieva, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Ligand-mediated transport of drug delivery devices across the blood-brain barrier

Promotor(s): prof. D. Hoekstra

Faculty: Medical Sciences

The bottleneck for successful drug delivery into the brain is the blood-brain barrier (BBB), a physical and metabolic barrier. Nanoparticles represent drug delivery devices, that - when linked to proper targeting ligands - may penetrate the BBB and hence increase the bioavailability of medicines into the brain. Moreover, a therapeutic molecule can be incorporated in a nanoparticle, protecting if from degradation during transport to the site of action. In this project, the cellular prion protein and the monosialoganglioside GM1 as blood-brain barrier receptors were characterized regarding their potential to induce receptor-mediated transcytosis of ligand-modified nanoparticles. Novel short peptidic ligands that bind to either prion or GM1 generated phage display and grafted on the surface of polymeric nanoparticles. Nanoparticles decorated with a GM1-binding peptide showed a brain-targeting potential in vivo, together with a high transcytotic capacity in vitro and in vivo, which makes them a promising vehicle for drug delivery into the brain.