Designing the future of nanomedicine: Current barriers to targeted brain therapeutics

Abstract

Access of therapeutic agents to the central nervous system is generally restricted by an intricate barrier system, which protects the brain and maintains homeostasis. Endogenous nutrients, however, engage with the available molecular systems and successfully cross the blood-brain barrier (BBB). One of the systems, receptor-mediated transcytosis (RMT), involves non-stereoselective vesicular trafficking and has been extensively investigated as suitable for transportation of large molecular cargos. This review focuses on recent developments in elucidating the molecular pathways that regulate RMT and the fashion in which they impact the design of therapeutic nanosystems for BBB transcytosis. The challenges of brain targeting, however, are not restricted to successful engagement with BBB receptors, also including species-specificity, selectivity and maintaining targeting capability in real biological media.