The monoclonal antibodies (mAbs) are promising therapeutic agents for the treatment of neurological disorders, due to their high specificity. Their clinical application, however, is significantly hampered by their poor transport across the blood-brain barrier (BBB) and through its difficult to disseminate within the brain parenchyma.
Researchers from the Singular Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) of the University of Santiago de Compostela and of the Santiago de Compostela Health Research Institute (IDIS), among them the expert of the Chair in Science and Society María José Alonso, have developed and evaluated two structurally distinct nanosystems for mAb delivery to the brain: pegylated polyglutamic acid nanocapsules and based nanoassemblies.
So far, health research efforts have been mainly oriented towards overcoming the blood-brain barrier, while the challenge of efficient diffusion in the brain remains largely unexplored, as explained in their article, titled "The challenge of efficient diffusion in the brain". “Delivery of monoclonal antibodies to the brain: the impact of nanocarrier structure”.” and published in Drug Delivery and Translational Research.
CiMUS and IDIS researchers have succeeded in efficiently encapsulating the mAb bevacizumab model in the two nanosystems developed, which they showcased below, different physico-chemical properties. While the pegylated polyglutamic acid nanocapsules showed a size of 80 nm and a neutral zeta potential, the PGAC14-based nanoassemblies showed an ultra-small size of 40 nm and a negative surface charge.
Based on these results, and after assessing their diffusion capacity by immunofluorescence, the team concluded that the latter were more efficient and showed a favourable neuroinflammatory profile. This is probably due to their small size and negative charge, The BVZ is a highly selective, intracellularly interacting and delivering BVZ intracellularly to neuronal cells following intraparenchymal administration.
In their conclusion, the authors argue that “these findings provide key information on the optimisation of nanocarrier design to improve mAb delivery to the brain”.